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Dissertations / Theses on the topic 'Neuromuscular transmission'

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Published: 4 June 2021
Last updated: 31 July 2024

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1

Carvalho, Vanessa Henriques 1974. "Ação dos anestésicos locais na transmissão neuromuscular e influência no bloqueio produzido pelo pancurônio : eficácia da neostigmina e da 4-aminopiridina na reversão do bloqueio neuromuscular: estudo experimental." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312496.

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Orientador: Angélica de Fátima de Assunção Braga
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Os anestésicos locais (AL) podem interagir com os bloqueadores neuromusculares (BNM) e modificar as suas propriedades farmacocinéticas e farmacodinâmicas, no entanto o mecanismo dessa interação é controverso. Este estudo experimental, realizado em preparações nervo frênico - hemidiafragma de rato e músculo biventer cervicis de pintainho, teve por objetivo avaliar o efeito de diferentes AL na transmissão neuromuscular e sua influência no bloqueio produzido pelo pancurônio. Foram avaliados os seguintes parâmetros: efeito na transmissão neuromuscular dos AL (ropivacaína, levobupivacaína, mistura em excesso enantiomérico de bupivacaína) e do pancurônio empregados isoladamente; o bloqueio produzido pelo pancurônio em preparações previamente expostas aos AL; a eficácia da neostigmina e da 4-aminopiridina na reversão do bloqueio neuromuscular produzido pelo pancurônio isoladamente e em preparações previamente expostas aos AL; a ação dos AL na resposta contraturante à acetilcolina; seus efeitos nos potenciais de membrana e nos potenciais de placa terminal em miniatura. Os resultados foram expressos em médias e desvios padrão e analisados através dos testes t de Student, Wilcoxon, Anova, Kruskall-Wallis e Mann-Whitney. Adotou-se um nível de significância de 5% (p<0,05). Na preparação nervo frênico - hemidiafragma de rato, os AL nas concentrações empregadas, não alteraram a amplitude das respostas musculares mas, potencializaram o efeito do pancurônio. O bloqueio neuromuscular foi parcial e totalmente revertido com a neostigmina e com a 4-aminopiridina, respectivamente. Não causaram alteração significativa nos potenciais de membrana e produziram diminuição progressiva na amplitude e na frequência dos potenciais de placa terminal em miniatura. Na preparação biventer cervicis de pintainho os AL, com exceção da ropivacaína, promoveram diminuição na resposta contraturante da acetilcolina. Os resultados obtidos neste estudo demonstram um sinergismo entre os fármacos estudados, resultante das ações pré e pós-juncionais dos anestésicos locais
Abstract: Local anaesthetics (LA) may interact with neuromuscular blockers and modify their pharmacokinetic and pharmacodynamic properties. However, the mechanism of this interaction is controversial. This experimental study, conducted in rat phrenic nerve diaphragm preparations and chick biventer cervicis, aimed to evaluate the effect of different LA in neuromuscular transmission and its influence on pancuronium induced blockade. The following parameters were evaluated: the effect on neuromuscular transmission of LA (ropivacaine , levobupivacaine mixture enantiomeric excess bupivacaine) and pancuronium used in isolation; the blockade produced by pancuronium in preparations previously exposed to LA; the effectiveness of neostigmine and 4 - aminopyridine in the reversal of neuromuscular blockade produced by pancuronium alone and in preparations previously exposed to AL; the action of LA in the contractile response to acetylcholine; its effects on membrane potentials and miniature endplate potentials. The results were expressed as means and standard deviations and analyzed using Student's t, Wilcoxon, ANOVA, Kruskal-Wallis and Mann-Whitney tests. A significance level of 5 % (p < 0,05) was adopted . In the rat phrenic nerve diaphragm preparation the LA, in the concentrations used, did not alter the amplitude of muscle response but potentiated the effect of pancuronium. Neuromuscular blockade was partially and fully reversed with neostigmine and 4- aminopyridine, respectively. There was no significant change in membrane potential and a progressive decrease in the amplitude and frequency of miniature endplate potentials was produced. In the chick biventer cervicis preparation the LA, with the exception of ropivacaine, led to a decrease in the contractile response to acetylcholine. The results of this study demonstrate a synergistic effect between the drugs studied, resulting from prejunctional and postjunctional actions of LAs
Doutorado
Farmacologia
Doutora em Farmacologia
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2

England, Adrian James. "The effect of moderate hypothermia on neuromuscular transmission and neuromuscular blockade." Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338687.

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3

Kalliomäki, Jarkko. "Parallel processing of nociceptive information evidence for multiple reflex and ascending nociceptive pathways /." Lund : Dept. of Physiology and Biophysics, University of Lund, 1992. http://books.google.com/books?id=PMlqAAAAMAAJ.

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4

Dusl, Marina. "Novel pathomechanisms implicated in defects of neuromuscular transmission." Diss., Ludwig-Maximilians-Universität München, 2015. http://nbn-resolving.de/urn:nbn:de:bvb:19-180274.

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5

Budd, Timothy Charles. "An immunological investigation of neuromuscular transmission in insects." Thesis, University of Nottingham, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.334782.

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6

Luheshi, G. N. "Diabetes in the rat and postganglionic neuromuscular transmission." Thesis, University of Newcastle Upon Tyne, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287330.

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7

Dissanayake, Kosala Nimanthi. "Evaluation of neuromuscular transmission in organophosphorus pesticide toxicity." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/15837.

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Organophosphorus (OP) pesticide toxicity is a global health problem. Respiratory failure due to neuromuscular transmission dysfunction accounts for about 300,000 deaths annually in rural Asia. However, the clinical manifestation is complex, and described in terms of acute, intermediate, and chronic syndromes. The underlying mechanism of toxicity is still unclear. OP pesticides contain inhibitors of acetylcholinesterase (AChE), for example dimethoate, emulsified in an organic solvent, typically cyclohexanone. A hypothesized mechanism is initial excitotoxicity through inhibition of acetylcholinesterase followed by failure of neuromuscular synaptic transmission. I tested this electrophysiologically in vitro by measuring properties of spontaneous miniature endplate potentials (MEPPs) and evoked endplate potentials (EPPs) in isolated sciatic nerve/flexor digitorum brevis muscles from mice, bathed in HEPES-buffered mammalian physiological saline (MPS). Muscle action potentials were abolished with μ-conotoxin (2μM). First, we tested the effects of plasma taken from Göttingen minipigs instilled orally (isofluorane anaesthesia) with a formulated pesticide (2.5ml/kg) whose active ingredient is dimethoate dissolved in cyclohexanone. This plasma abolished evoked synaptic transmission and increased spontaneous MEPP frequency within 60-180 minutes of bath application. However plasma from minipigs instilled with dimethoate alone produced no failure of transmission. Plasma contained either pesticide or dimethoate significantly increased the half decay time of EPPs. However, pesticide-plasma also contained the metabolites omethoate (100μM) and cyclohexanol (5 mM). We found that bath application of omethoate alone caused a potent dose-dependent increase in EPP decay time. Cyclohexanol (5 mM) also increased EPP decay time but it also decreased both the excitability of axons and MEPP amplitude. In combination, omethoate and cyclohexanol produced greater disruption of neuromuscular transmission than either dimethoate or cyclohexanone, alone or in combination and this was particularly evident in isometric tension recordings, in which prolonged after-contraction and slow relaxation were observed during and immediately following tetanic stiumuation in the presence of omethoate and cyclohexanol. Voltage-clamp recordings of endplate currents (EPC) partially supported the EPP observations. Surprisingly, cyclohexanol-treated preparations showed no significant increase in EPC and MEPC decay time. However, there was some evidence of activity-dependent decline in MEPC amplitude in cyclohexanol while quantal content in these preparations showed evidence of an increase suggesting a homeostatic response in evoked transmitter release with cyclohexanol treatment. Analysis of presynaptic currents in cyclohexanol treated preparations also revealed preliminary evidence of sensitivity to cyclohexanol compared to control preparations. Finally, I tested the effects NMJ transmission of 24hr exposure to OP pesticide and its metabolites using a novel organ culture system, utilising a mouse mutant (WldS) with a slow nerve degeneration phenotype. After incubation of 24 hrs with MPS + pesticides and metabolites, these muscles showed significant reduction in function (response to nerve stimuli with EPP/action potential ± MEPPs) compared to control cultures. Together, the data indicate that failure of neuromuscular transmission by pesticide-plasma cannot be explained solely by dimethoate-mediated inhibition of acetylcholinesterase. Rather, a combination of metabolic breakdown products exerts potent, harmful presynaptic and postsynaptic effects. Either blocking the metabolic conversion of the constituents of OP pesticides, or transiently blocking their effects on receptors may therefore be an effective strategy for treatment of OP pesticide toxicity.
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8

Morgan, Gareth P. "Neuromuscular transmission in murine muscular dystrophy (129 ReJ strain)." Thesis, Aston University, 1985. http://publications.aston.ac.uk/12486/.

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9

Zhu, Chuan. "Src signaling in neuromuscular junction induction /." View abstract or full-text, 2010. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202010%20ZHU.

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10

Loyola, Yolanda Christina de Sousa. "Influencia dos anestesicos locais no bloqueio neuromuscular produzido por diferentes bloqueadores neuromusculares : estudo experimental." [s.n.], 2006. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310900.

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Orientador: Angelica de F. de Assunção Braga
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Os anestésicos locais comumente empregados na prática clínica podem interagir com os bloqueadores neuromusculares e potencializar seus efeitos. Muitos autores estudaram esta interação mas o mecanismo envolvido na potencialização do bloqueio neuromuscular e a ação dos anestésicos locais nos sítios pré e pós juncionais não foram completamente elucidados. Neste trabalho através de experimentos específicos na junção neuromuscular foram estudados os seguintes parâmetros: o efeito dos anestésicos locais procaína e lidocaína na transmissão neuromuscular; a sua influência no bloqueio neuromuscular produzido pela d-tubocurarina e pelo rocurônio; a eficácia da neostigmina e da 4-aminopirídina na reversão do bloqueio produzido pela associação anestésicos locais - bloqueadores neuromusculares; os efeitos dos anestésicos locais nos potenciais de membrana e potenciais de placa terminal em miniatura. Avaliou-se também em preparações diafragma de rato cronicamente desnervado e biventer cervicis de pintainho os efeitos dos anestésicos locais na ação contraturante da acetilcolina. Os resultados foram expressos em médias e desvios padrão e analisados através dos testes de Wilcoxon e Mann-Witney, adotando-se um nível de significância de 5% (p < 0,05). Nas preparações nervo frênico - diafragma de rato, sob estimulação elétrica indireta, os anestésicos locais nas concentrações empregadas, não alteraram a amplitude das respostas musculares mas potencializaram os efeitos da d- tubocurarina e do rocurônio.. Este bloqueio foi parcialmente e totalmente revertido pela neostigmina e pela 4-aminopiridina, respectivamente. A procaína e a lidocaína não causaram alteração significativa nos potenciais de membrana, não demonstrando ação despolarizante na fibra muscular. A procaína causou diminuição na amplitude e na freqüência dos potenciais de placa terminal em miniatura (pptms) e a lidocaína, ao contrário, promoveu um aumento inicial na freqüência dos pptms seguida de bloqueio. Nas preparações biventer cervicis de pintainho e diafragma de rato cronicamente desnervado, a procaína e a lidocaína promoveram diminuição significativa na resposta contraturante da acetilcolina evidenciando um efeito pós-juncional. Os resultados obtidos demonstram um sinergismo entre as drogas devido principalmente a um efeito pós-juncional
Abstract: Local anesthetics commonly used in clinical practice can interact with neuromuscular blockers and potentiate their effects. Many authors studied this interaction, but the mechanism involved in the potentiation of neuromuscular blockers and the action of local anesthetics in the pre and postjunctional sites were not completely elucidated- In this study, in specific experiments in the neuromuscular junction the following parameters were studied: the effects of the local anesthetics procaine and lidocaine in the neuromuscular transmission; its influence on the neuromuscular blockade produced by d-tubocurarine and by rocuronium; the efficacy of neostigmine and of 4-aminopyhdine in the reversion of the blockade produced by the association of local anesthetics - neuromuscular blockers; the effects of local anesthetics on the membrane potentials and miniature end - plate potentials. It was also evaluated in chronically denervated rat diaphragm preparation and chick biventer cervicis preparation the effects of local anesthetics on acetylcholine contracture. The results were expressed in average and standard deviation and analyzed through the Wilcoxon and Mann-Witney tests, adopting a level of significance of 5% (p <0.05). In rat phrenic nerve diaphragm preparations under indirect electric stimulation, local anesthetics in the concentrations used did not change the amplitude of the muscle response but potentiated the effects of d-tubocurarine and of rocuronium. This blockade was partially and totally reverted by neostigmine and by 4-aminopyridine, respectively. Procaine and lidocaine caused no significant alteration in the membrane potentials, not demonstrating depolarizing action in the muscle fiber. Procaine caused a decrease in the amplitude and frequency of the miniature end - plate potentials {meps) and lidocaine, in contrast, promoted an initial increase in the frequency of meps followed by blockade. In chick biventer cervicis preparations and chronically denervated rat diaphragm, procaine and lidocaine promoted a significant decrease in the response to acetylcholine contracture evidencing a post-junctional effect. The results obtained demonstrate a synergism among the drugs mainly due to a postjunctional effect
Doutorado
Doutor em Farmacologia
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11

Betty, Maria. "Molecular genetic studies in hereditary myasthenia." Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.240536.

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12

Spillane, J. "Clinical and functional studies of autoimmune disorders of neuromuscular transmission." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1461232/.

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Inherited and acquired disorders of the neuromuscular junction are an important cause of muscle weakness and fatigability. In this thesis I focus on the autoimmune disorders of neuromuscular transmission. Myasthenia Gravis (MG) is the most common of these diseases and is typically caused by antibodies against the post-synaptic acetylcholine receptor. Lambert Eaton Myasthenic Syndrome (LEMS) is a pre-synaptic disorder typically caused by antibodies against voltage gated calcium channels (VGCC). With regard to LEMS, my main aim was to gain a more complete understanding of the pathomechanisms of the disease. To date, the direct effect of LEMS IgG on presynaptic neurotransmitter release had not been investigated in detail. I examined how LEMS IgG affects neurotransmitter release by imaging action potential dependent vesicle exocytosis using a fluorescent dye. I found that LEMS IgG significantly inhibited the rate of synaptic vesicle release but this effect was lost in synapses from a Cacna1a knockout mouse. These data provide direct evidence that LEMS is caused by impaired neurotransmitter release due to an effect on P/Q-type VGCCs. With regard to MG, I studied the long-term outcome of patients with thymomatous and non-thymomatous MG after thymectomy and found that in general the outcome was favourable in the majority of patients with 34% of patients achieving complete stable remission. I also reviewed the long-term outcome of patients after a severe exacerbation of MG requiring ITU admission. Despite the significant mortality associated with severe exacerbations of MG, it was found that specialised neuro-intensive care was associated with a good long-term prognosis in the majority of patients. There were no significant differences in outcome in those with early or late onset MG. Overall the data presented in this thesis provide new insights into the pathomechanisms of LEMS IgG and provide new information regarding the long-term outcome of patients with MG.
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13

Claus, Gabriel Machado. "Drop jump promove melhora no desempenho de RSA, mas não em parâmetros neuromusculares em jogadores jovens de basquete /." Bauru, 2019. http://hdl.handle.net/11449/190777.

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Orientador: Alessandro Moura Zagatto
Banca: Paulo Henrique Silva Marques de Azevedo
Banca: Julio Wilson dos Santos
Resumo: Em modalidades esportivas coletivas como o basquete, a aptidão em realizar sprints repetidos vem se demonstrando um fator físico determinante. A alta intensidade exigida durante toda a partida irá induzir uma incapacidade de manutenção dos níveis de velocidade/força iniciais, diminuindo o desempenho e, consequentemente, instaurando a fadiga muscular. Uma estratégia para o aumento do desempenho pode ser a potenciação pós ativação (PPA). A PPA consiste no aumento involuntário dos níveis de contração muscular em resposta a um estímulo voluntário anterior e vem sendo inserida na rotina de aquecimento levando a melhoria do desempenho. Ainda, a PPA vem sendo mais efetiva quanto maior a especificidade ao modo de exercício, em comparação a potenciação com atividades menos específicas a atividade requerida. Assim, o objetivo do presente estudo foi investigar o efeito de protocolos de esforços condicionantes específicos sobre o desempenho nos esforços de sprints repetidos (RSA) com mudanças de direção em atletas de basquete e sobre parâmetros da fadiga muscular. Participaram do estudo 10 atletas de basquete (idade: 17,5 ± 1,2 anos; estatura: 1,9 ± 0,1 m; peso: 87,2 ± 15,4 kg; experiência competitiva: 5,2 ± 1,5 anos), que realizaram os procedimentos experimentais de modo cruzado e randômico. Inicialmente os voluntários foram familiarizados com os procedimentos, nas demais visitas de avaliações os voluntários foram submetidos a um aquecimento padronizado, idênticos em todas as condições.... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Repeated sprint efforts have been identified as a key component of physical fitness in team sports, such basketball. The high intensity efforts required throughout the game will generate fatigue, and the inability to maintain initial velocity/force levels, thus, decreasing performance and hence instituting muscle fatigue. A strategy to improve performance can be post-activation potentiation (PAP). PAP is defined as enhanced involuntary twitch in response of a prior voluntary contraction and has been inserted into the warm-up routine leading to improved performance. In addition, specific PAP application to mode of exercise showed better results than a PAP non-specific to sport. Therefore, the objective of this present study was to investigate the effect of two specifics PAP protocols on performance in repeated sprint efforts with changes on direction in basketball players and in fatigue manifestation. Ten basketball players (age: 17,5 ± 1,2 years; height: 1,9 ± 0,1 m; weight: 87,2 ± 15,4 kg; competitive experience: 5,2 ± 1,5 years) were selected and participated in randomized cross over mode experimental procedures. Initially, the volunteers were familiarized with the procedures, in the next visits of evaluations the volunteers were submitted to a standardized warm-up, identical in all the conditions. After warming up, neuromuscular measurements were performed, consisting of 2 contractions voluntary maximal isometric of knee extension with electrical stimuli and monitoring of ... (Complete abstract click electronic access below)
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14

Ferreira, Sandro Rostelato 1982. "Efeitos do veneno de Rhinella schneideri sobre a junção neuromuscular." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308658.

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Orientador: Léa Rodrigues Simioni
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Rhinella schneideri, conhecido previamente como Bufo paracnemis, é um sapo comum em muitas regiões do Brasil. O veneno destas espécies exerce importante efeito cardiovascular em humanos e animais, mas pouco se sabe sobre sua atividade neuromuscular. Neste trabalho, nós avaliamos a neurotoxicidade do veneno de R. schneideri em preparações neuromusculares de pintainho e camundongo. Através da compressão manual das glândulas parótidas localizadas atrás dos olhos, coletou-se a secreção e então realizada a extração com metanol. O extrato metanólico foi liofilizado e testado em preparações biológicas. Preparações biventer cervicis (BC) de pintainho e nervo frênico diafragma (NFD) de camundongo foram utilizadas para o registro miográfico através de estimulação elétrica indireta para medidas eletrofisiológicas, análise morfológica e microscopia eletrônica de transmissão. Frações ativas do extrato metanólico foram obtidas submetendo-se à coluna de fase reversa Luna PFP (250 x 4,6 mm). O extrato metanólico (50 ?g/ml) causou somente facilitação da neurotransmissão em preparações NFD. Ao contrário, causou bloqueio neuromuscular significativo em preparações BC que foram concentração-dependente (3, 10 and 30 ?g/ml; a 37º C) com tempo para 50% de bloqueio, média ± erro padrão: 84±10, 51±3 e 12±0,8 min com 3, 10 e 30 ?g/ml, respectivamente; n=6-8 cada, precedido por facilitação da neurotransmissão. Não houve inibição significativa das respostas contraturantes à ACh (110 ?M) ou KCl (20 mM) após bloqueio completo em qualquer concentração testada. Em preparações BC incubadas com o extrato metanólico (10 ?g/ml) a 22º C por 70 min não observou-se qualquer alteração das respostas musculares (117±3%; n=5), mas quando a temperatura do banho foi elevada a 37º C, 50% de bloqueio ocorreu após 92±3 min (n=5; p<0.05). A incubação de preparações BC curarizadas (d-Tc, 1 ?g/ml) com o extrato metanólico (10 ?g/ml) resultou em completo e irreversível bloqueio enquanto que as preparações tratadas somente com curare mostraram a reversão completa da resposta contrátil após várias lavagens. Não houve aumento significativo nos níveis de liberação de creatinoquinase (90±21 vs. 80±15 U/l, antes e após 120 min de incubação com o extrato, respectivamente, n=5) além da ausência de alterações na morfologia das fibras musculares ou na porcentagem de danos na fibra (2.4±0.9 vs. 2.3±0.5 %, antes e após 120 min de incubação com o extrato, respectivamente, n=5). O extrato metanólico (50 ?g/ml) aumentou a resposta contrátil mas não alterou o potencial de membrana em repouso (-81±1 mV e -78±1 mV para controle e preparação tratada após 60 min). Registros eletrofisiológicos mostraram que houve um aumento progressive na frequência dos potenciais de placa terminal em miniatura (PPTM) de 34±3,5 (controle) para 88±15 (após 60 min de incubação com o extrato); houve também um aumento nos valores do conteúdo quântico, de 128±13 (controle) para 272±34 e 171±11 após 5 min e 60 min, respectivamente, em preparações tratadas com o extrato metanólico. A microscopia eletrônica de transmissão mostrou que o volume ocupado pelas vesículas sinápticas foi significativamente reduzida (32±5%; p<0.05) após 5 min mas este efeito foi reversível após 60 min de incubação para as preparações tratadas com 50 ?g/ml do extrato metanólico. Não houve dano estrutural distinguível na membrana do terminal nervoso e nas mitocôndrias das preparações tratadas com o extrato, quando comparada com as preparações controle. O pré-tratamento das preparações NFD com ouabaína (1 ?g/ml), um inibidor da bomba de Na+/K+-ATPase, por 5 min antes da incubação com o extrato, preveniu o aumento do conteúdo quântico comparado com preparações controle (118±18, 117±18 e 154±33 para preparações controle-ouabaína e tratadas com ouabaína e incubadas com o extrato por 5 min e 60 min, respectivamente). A cromatografia por HPLC do extrato metanólico resultou em 24 frações, das quais 4 (frações 20, 21, 22 e 24) causaram bloqueio neuromuscular em preparações BC. A fração 20 (3 ?g/ml) foi escolhida por ser 3 vezes mais potente que as demais e causou bloqueio neuromuscular significativo (p<0.05; tempo para 50% de bloqueio: 43±4 min; n=4) precedido por facilitação em preparações BC a 37º C. A fração 20 não inibiu as respostas contraturantes à ACh (110 ?M) ou KCl (20 mM) após completo bloqueio neuromuscular em preparações BC. Em preparações NFD, a fração (15 ?g/ml) aumentou significativamente os valores do conteúdo quântico de 117±18 (controle) para 236±44 após 5 min de incubação (n=4; p<0.05). Estes resultados indicam que o extrato metanólico do veneno de R. schneideri é capaz de interferir com a neurotransmissão por ativar e/ou bloquear a liberação da acetilcolina nos sítios pré-sinápticos, provavelmente envolvendo a bomba de Na+-K+-ATPase, sem causar qualquer dano à musculatura
Abstract: Rhinella schneideri, previously known as Bufo paracnemis, is a common toad in many regions of Brazil. The venom of this species exerts important cardiovascular effects in humans and animals, but little is known of its neuromuscular activity. In this work, we examined the neurotoxicity of R. schneideri venom in chick and mouse neuromuscular preparations. Venom was collected by manual compression of the large parotid glands behind the eyes and then extracted with methanol. The extract was lyophilized prior to testing in biological preparations. Chick biventer cervicis (BC) and mouse phrenic nerve-diaphragm (PND) preparations were mounted for conventional twitch-tension recording in response to indirect stimulation, for electrophysiological measurements, morphological analysis and transmission electronic microscope. Also, an active fraction of this methanolic extract obtained by reverse phase HPLC on a Luna PFP (250 x 4.6 mm) column. The methanolic extract (50 ?g/ml) caused facilitation but no neuromuscular blockade in PND preparations. In contrast, significant (p<0.05) concentration-dependent (3, 10 and 30 ?g/ml) neuromuscular blockade (time for 50% blockade, mean±S.E.M.: 84±10, 51±3 and 12±0.8 min with 3, 10 and 30 ?g/ml, respectively; n=6-8 each) preceded by facilitation was seen in BC preparations at 37oC. There was no inhibition of contractures to exogenous ACh (110 ?M) or KCl (20 mM) after complete blockade by any of the concentrations tested. Incubation of BC preparations with methanolic extract (10 ?g/ml) at 22oC for 70 min did not affect neuromuscular transmission (117±3%; n=5), but when the bath temperature was increased to 37oC, 50% blockade occurred within 92±3 min (n=5; p<0.05). Incubation of curarized (d-Tc, 1 ?g/ml) BC preparations with methanolic extract (10 ?g/ml) resulted in complete, irreversible blockade whereas preparations treated with curare alone showed complete reversion in the twitch-tension after washing. There was no significant increase in creatine kinase levels (90±21 vs. 80±15 U/l, before and after a 120 min incubation with extract, respectively; n=5) and no significant alterations in muscle fiber morphology or in the percentage of damaged fibers (2.4±0.9 vs. 2.3±0.5 % before and after a 120 min incubation with extract, respectively; n=5). The methanolic extract (50 ?g/ml) increased the twitch-tension but did not alter the membrane resting potential (-81±1 mV and -78±1 mV for control and poison-treated preparations after 60 min). Electrophysiological measurements showed that there was a progressive increase in the frequency of miniature end-plate potentials (MEPPs) from 34±3.5 (control) to 88±15 (after a 60 min incubation with extract); there was also an increase in the end-plate potentials (based on the quantal content) from 128±13 (control) to 272±34 and 171±11 after 5 min and 60 min, respectively, in extract-treated preparations. TEM showed that the fractional volume occupied by synaptic vesicles was significantly reduced (32±5%; p<0.05) after a 5 min but this effect was reversible after 60 min of incubation to 50 ?g/ml of methanolic extract. There was no structural damage to the membrane of the terminal boutons and the mitochondria of extract-treated preparations were indistinguishable from those of control preparations. Pretreatment of the preparations with ouabain (1 ?g/ml), a Na+/K+-ATPase pump inhibitor, for 5 min prior to incubation with methanolic extract prevented the increase in quantal content compared to preparations without extract (118±18, 117±18 and 154±33 for ouabain-treated controls and ouabain-treated preparations incubated with venom for 5 min and 60 min, respectively). HPLC of the methanolic extract resulted in 24 fractions, of which four (fractions 20, 21, 22 and 24) produced blockade in BC preparations. Fraction 20 (3 ?g/mL) was chosen because was the most potent of the four fractions and caused significant (p<0.05) neuromuscular blockade (time for 50% blockade: 43±4 min; n=4; mean±SEM) preceded by facilitation in BC preparations at 37oC. Fraction 20 did not inhibit contractures to exogenous ACh (110 ?M) or KCl (20 mM) after complete neuromuscular blockade in BC preparations. In PND preparations, fraction 20 (15 ?g/mL) significantly increased the quantal content value from 117±18 (control) to 236±44 after 5 min (n=4; p<0.05). These results indicate that the methanolic extract of R. schneideri is capable to interfere with the neurotransmission by activing and/or blocking the pre-synaptic acetylcholine release by an activity involving the Na+-K+-ATPase pump, without damaging the muscle membrane
Doutorado
Farmacologia
Doutor em Farmacologia
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15

Henaghan, Sharon M. "The effects of moderate sleep loss on sleepiness levels and neuromuscular function in healthy males a thesis submitted to Auckland University of Technology in partial fulfillment of the degree of Master of Health Science, April 2004." Full thesis. Abstract, 2004. http://puka2.aut.ac.nz/ait/theses/HenaghanS.pdf.

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16

Mañé, Reed Noemí. "Neuromuscular transmission in the gastrointestinal tract and its interaction with pacemakers." Doctoral thesis, Universitat Autònoma de Barcelona, 2016. http://hdl.handle.net/10803/393991.

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L'intestí gros desenvolupa una varietat de funcions essencials per a una utilització òptima dels aliments. Es necessiten diferents tipus de patrons de motilitat per dur a terme aquestes funcions i, en aquesta tesi, el nostre objectiu ha estat augmentar la comprensió dels mecanismes subjacents a la seva regulació. La coordinació temporal i espacial de les contraccions i relaxacions del múscul llis donen lloc als diferents patrons motors. El múscul llis està sota el control de dos sistemes: el Sistema Nerviós Entèric i les xarxes de Cèl·lules Intersticials de Cajal (ICC). Els principals transmissors alliberats per les motoneurones entèriques inhibitòries són l’ATP i l'òxid nítric (NO). En aquest treball, hem descrit com les diferents freqüències de descàrrega de les neurones determinen l'acció d'un o altre co-transmissor. Ràfegues curtes o de baixa freqüència causen principalment respostes purinèrgiques mitjançant l’activació de receptors P2Y1 (bloquejades per BPTU, un nou antagonista al·lostèric del receptor P2Y1), mentre que les ràfegues llargues a altes freqüències potencien la neurotransmissió nitrèrgica. Això es deu a què la neurotransmissió purinèrgica s’atenua amb a altes freqüències i per tant, aquesta via només és capaç de causar relaxacions transitòries. La neurotransmissió nitrèrgica, per contra, pot relaxar el còlon de manera sostinguda. D'acord amb això, les respostes nitrèrgiques són predominants al còlon proximal, on té lloc l'emmagatzematge dels efluents de l’ili i l'absorció d'aigua i altres substàncies. En canvi, el gradient de la neurotransmissió purinèrgica és invers i per tant, al còlon distal, responsable de la propulsió de femtes, hi predominen les relaxacions transitòries. La neurotransmissió inhibitòria pot modular la ritmicitat miogènica generada per les ICCs. Mentre que les ones lentes, originades per les ICC del plexe submuscular de còlon (ICC-SMP), semblen ser resistents a la hiperpolarització, les despolaritzacions cícliques desenvolupades per les ICCs del plexe mientèric (ICC-MY) desapareixen quan el potencial de membrana baixa per sota de -40 mV a causa de la seva dependència dels canals de calci de tipus L. Per tant, per tal de permetre el desenvolupament d'aquest marcapàs, el potencial de membrana a la zona on es generen les despolaritzacions cícliques és al voltant de -40 mV. En canvi, les cèl·lules del múscul llis properes al plexe submuscular tenen un potencial de membrana al voltant de -50 mV, és a dir, existeix un gradient transmural. En conseqüència, l'amplitud de les respostes inhibitòries també mostra un gradient. Les ones lentes són registrades en viu com contraccions d'alta freqüència i d'amplitud relativament baixa (“ripples”); mentre que les despolaritzacions cícliques s'han associat a contraccions de propulsió i creiem que són també la base miogènica de les contraccions d'alta amplitud conegudes com a HAPC induïdes via neural. In vitro, s'ha observat un tercer patró motor que consisteix en un “wax and wane” (créixer i minvar) de les contraccions associades a ones lentes. És molt probable que el “wax and wane” es degui a una modulació del marcapàs del ICC-SMP per part del marcapàs de l'ICC-MY. Creiem que aquest patró és la base dels contraccions individuals (“single motor patterns”) observats amb manometria d’alta resolució. En conclusió, la contribució d'ATP i NO a la relaxació depèn de la freqüència de descàrrega de les motoneurones inhibitòries. Els co-transmissors mostren diferents rols funcionals i estan distribuïts al llarg del còlon en conformitat amb el paper de cada regió. Malgrat les ICCs estableixen la ritmicitat de les contraccions a través dels marcapassos, les neurones entèriques recopilen informació del contingut luminal i potencien o inhibeixen els marcapassos i/o produeixen relaxacions o contraccions en les diferents àrees per tal d'optimitzar el processament del contingut.
The large intestine performs a variety of functions essential for an optimal use of food. Different types of motility patterns are needed to develop these functions and, in this thesis, our aim has been to increase the understanding of the mechanisms underlying their regulation. The temporal and spatial coordination of smooth muscle contractions and relaxations results in the different motor patterns. Smooth muscle is under the control of two systems: the Enteric Nervous System and the Interstitial Cells of Cajal (ICC) networks. The major transmitter substances released by enteric inhibitory motor neurons are ATP and nitric oxide (NO). In this work, we have described how different neuronal firing frequencies are responsible for the action of one or another co-transmitter. Short bursts or low frequencies cause mainly P2Y1 mediated purinergic responses (blocked by BPTU, a novel P2Y1 allosteric antagonist) while long bursts at high frequencies enhance nitrergic neurotransmission. This is due to the fact that purinergic neurotransmission attenuates with frequency-increase and therefore, this pathway is only able to cause transient relaxations. Nitrergic neurotransmission, in contrast, can relax colonic tissue in a sustained manner. Accordingly, nitrergic responses are predominant in the proximal colon where storage of ileal effluents and absorption of water and other substances take place. Contrarily, the gradient of purinergic neurotransmission is inverse and therefore, transient relaxations predominate in the distal colon. Inhibitory neurotransmission can modulate the myogenic rythmicity generated by ICCs. Whereas slow waves, originated in the colonic ICCs of the Submuscular Plexus (ICC-SMP), appear to be resistant to mild hyperpolarisations, cyclic depolarizations developed by the ICC of the Myenteric Plexus (ICC-MY) disappear when the membrane potential goes under -40 mV due to their dependence on L-type calcium channels. Therefore, in order to allow the development of this pacemaker, the resting membrane potential (RMP) in the area were cyclic depolarizations occur is around -40 mV. In contrast, smooth muscle cells near the submuscular plexus have a RMP of around -50 mV, i.e., a transwall gradient exists. In consequence, the amplitude of inhibitory responses is also graded. Slow waves can be recorded in vivo as “ripples”: high frequency contractions of relatively low amplitude; while cyclic depolarizations have been associated to propulsive contractions and we believe they are also the myogenic basis of neural induced high amplitude propagating contractions. In vitro, we have observed a third motor pattern that consists in a wax and wane of slow waves associated contractions. The wax and wane is very likely due to a modulation of the ICC-SMP pacemaker by the ICC-MY pacemaker. We believe this pattern is the basis of the single motor contractions observed with high resolution manometry. In conclusion, the relative contribution of ATP and NO to relaxation depends on the firing frequency of inhibitory motor neurons. They display different functional roles and are distributed along the colon accordingly. Although ICCs settle the rythmicity of contractions through their spontaneous cycling of the RMP, enteric neurons collect information of the luminal content and enhance or inhibit the pacemakers and/or produce relaxations or contractions in the different areas in order to optimize the processing of the content.
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17

Bucher, Daniel. "An Electrophysiological Analysis of Synaptic Transmission at the Drosophila Larval Neuromuscular Junction." Doctoral thesis, kostenfrei, 2008. http://www.opus-bayern.de/uni-wuerzburg/volltexte/2008/2778/.

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18

Emhemmed, Yousef Mohammed. "Maximum likelihood analysis of neuronal spike trains." Thesis, University of Glasgow, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326019.

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19

Trimble, Mark Herbert 1958. "EFFECTS OF ELECTRICAL STIMULATION ON THE RECRUITMENT ORDER OF MOTOR UNITS IN MAN: INDIRECT EXAMINATION BY ELECTRICALLY EVOKED MUSCLE RESPONSES." Thesis, The University of Arizona, 1987. http://hdl.handle.net/10150/276555.

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Although the neural mechanisms responsible for the orderly recruitment of motor units have been investigated extensively, the flexibility of the underlying neural circuitry remains unclear. For example, the effects of electrical stimulation on the recruitment order of motor units is not well understood. This project was designed to study the recruitment order of motor units in man during different stimulation protocols. Examination of the compound-twitch characteristics of electrically evoked responses allowed an indirect determination of motor-unit recruitment order. The results demonstrate that the recruitment order of quadriceps femoris and triceps surae motor units differs according to the stimulation protocols used. Analysis of the compound-twitch characteristics indicated that the recruitment order of motor units during Hoffmann reflexes is similar to that of volitional muscle contractions but effectively the reverse of that during direct-motor responses. Moreover, the results suggest that cutaneous-afferent stimulation alters the recruitment thresholds of different motor unit types during the Hoffman reflex.
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20

Dusl, Marina [Verfasser], and Robert [Akademischer Betreuer] David. "Novel pathomechanisms implicated in defects of neuromuscular transmission / Marina Dusl. Betreuer: Robert David." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2015. http://d-nb.info/1070762806/34.

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21

Chapman, Andrew Robert. "Neuromuscular control of the leg during cycling and running in triathletes /." [St. Lucia, Qld.], 2005. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe19326.pdf.

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22

Zhao, Xiaotao. "The role of protein phosphatase signaling in the formation of the neuromuscular junction /." View abstract or full-text, 2004. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202004%20ZHAO.

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23

Clark, David Rodney. "Neuromuscular assessment of trunk muscle function in loaded, free barbell back squat : implications for development of trunk stability in dynamic athletic activity." Thesis, University of Stirling, 2018. http://hdl.handle.net/1893/28080.

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Traditional core stability training was developed as a method of treating and preventing back pain. It was however, seamlessly applied to healthy and athletic populations without scientific evidence supporting its efficacy. Traditional core stability focussed on isolating and training the anatomical region between the pelvis and diaphragm, using isometric or low load exercises to enhance spinal stability. Scientific research challenged this approach for healthy function and athletic performance, resulting in a more functional anatomical definition, which included pelvic and shoulder girdles. Hence, a revised definition of dynamic trunk stability; the efficient coordination, transfer and resistance by the trunk, of force and power generated by upper and lower appendicular skeletal extremities during all human movement. This led to an integrated exercise training approach to dynamic trunk stability. Although early evidence suggested loaded compound exercises preformed upright, in particular back squat, were effective in activating and developing trunk muscles, evidence was inconclusive. Accordingly, the aims of this PhD were to investigate neuromuscular trunk function in loaded, free barbell back squat to understand training implications for trunk stability in dynamic athletic activity. Five research studies were conducted; 4 are published and 1 is being prepared for re-submission. The literature review revealed evidence that back squat was an effective method of activating trunk stabilzers and showed that these muscles were load sensitive (study 1). A survey of practitioners reported an understanding and appreciation of the challenge against core stability training for athletic populations. Furthermore, perceptions were aligned with growing evidence for dynamic and functional trunk stability training (study 2). A test-retest neuromuscular study established interday reliability and sensitivity of electromyographical measurement of trunk muscle activity in squats (study 3). Trunk muscle activation in back squat was higher than hack squat at the same relative, but lower absolute loads (study 4). Trunk muscle activation was lower in squats and bodyweight jumps in the strong compared to weak group (study 5). Furthermore, activation of the trunk muscles increased in each 30o segment of squat descent and was highest in first 30o segment of ascent for all loads (study 5). In conclusion, this series of studies confirmed acute effect of squats on trunk stabilizers and demonstrated that external load increases activation in these muscles. Parallel squat depth is important in optimizing trunk muscle activation. Finally, high levels of squat strength result in lower trunk muscle activation in loaded squats and explosive jumps.
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24

Chen, Cheng. "Presynaptic differentiation at the neuromuscular junction : regulation by a novel bFGF-p120 catenin signaling pathway /." View abstract or full-text, 2007. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202007%20CHEN.

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25

Clark, Merry C. "Monoaminergic receptors in the stomatogastric nervous system characterization and localization in Panulirus interruptus /." unrestricted, 2008. http://etd.gsu.edu/theses/available/etd-04212008-151237/.

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Thesis (Ph. D.)--Georgia State University, 2008.
Title from file title page. Deborah Baro, committee chair; Paul Katz, Charles Derby, Susanna Greer, Teryl Frey, committee members. Electronic text (249 p. : col. ill.) : digital, PDF file. Description based on contents viewed August 8, 2008. Includes bibliographical references (p. 222-249).
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26

Malfait, Nicole. "Characteristics of dynamics learning and generalization." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85577.

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In order to grasp an object, the human nervous system must transform the intended hand displacement into control signals distributed to motor neurons and ultimately to muscles. The aim of this thesis is to describe the nature of the internal representations that the human motor system uses to perform reaching movements.
The aim of the first study was to provide a clear and simple way to test whether dynamical information is coded by the nervous system in an extrinsic, Cartesian, versus intrinsic, muscle- or joint-based, system of coordinates. As a means to determine the frame for reference used by the motor system, we examined how adaptation to externally applied forces transfers across different arm configurations. We trained subjects to make reaching movements while holding a robotic arm that applied forces proportional and perpendicular to the tangential velocity of the hand. While in the first trials hand paths were substantially deviated, subjects rapidly adapted to the new dynamic condition; they learned to compensate for the forces in order to restore the kinematics observed in the absence of load. Learning of the new dynamics transferred across movements performed in different regions of the workspace when the relation between joint displacements and experienced torques remained unchanged, rather than when the mapping between hand displacements and forces was preserved. This provided support to the idea that dynamics are encoded in muscle- or joint-based coordinates.
The results of the first study described a process of generalization that relies on the invariance of the mapping between torques and joint displacements. While this clearly points to an intrinsic coding of dynamics, it does not explain whether or how generalization over the workspace occurs when the pattern of torques changes with the configuration of the arm. In the second study, subjects learned a force field in which the forces acted always in the same direction relative to an external frame of reference, which defines a mapping between joint displacements and torques that varies with the configuration of the arm. Our idea was to test if in the absence of invariance in the pattern of torques, generalization would occur on the basis of the invariance in the direction of the forces represented in an extrinsic system of coordinates. (Abstract shortened by UMI.)
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27

Sawant, Anagha Chandrasekhar Anand. "Cellular behaviors regulating tangential migration of facial branchiomotor neurons in the zebrafish embryo." Diss., Columbia, Mo. : University of Missouri--Columbia, 2009. http://hdl.handle.net/10355/6541.

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The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on January 20, 2010). Thesis advisor: Dr. Anand Chandrasekhar. Includes bibliographical references.
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28

Sole, Gisela, and n/a. "Neuromuscular control of thigh and gluteal muscles following hamstring injuries." University of Otago. School of Physiotherapy, 2008. http://adt.otago.ac.nz./public/adt-NZDU20081103.100628.

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Although traditional prevention and management strategies for hamstring injuries have focussed on optimising muscle strength, flexibility and endurance, incidence and/or recurrence rates of these injuries remains high. A theoretical framework was developed considering additional factors that increase the stabilising demand of the hamstrings. These factors included loss of related stability at the knee and lumbopelvic regions and extrinsic factors during functional and sporting activities. The aims of this research were to determine whether electromyographic (EMG) derived hamstrings, quadriceps and gluteal muscle activation patterns as well as isokinetic torque generation patterns could differentiate athletes who had incurred a hamstring injury from uninjured control athletes. It was hypothesised that the EMG activity of the injured participants would be decreased compared to uninjured control participants during maximal activities, but increased during weight bearing activities. The research included the identification of laboratory-based tasks relevant to the function of the hamstring muscles; test-retest reliability of EMG variables recorded during these tasks; and a comparative cross-sectional study of hamstring-injured (hamstring group, HG) and control athletes (control group, CG). Electromyographic activation patterns were determined during assessment of concentric and eccentric isokinetic strength of the thigh muscles, during transition from double- to single-leg stance, and forward lunging. Isokinetic and EMG onset and amplitude variables were compared both within- and between-groups. Despite no significant differences for peak torque, the HG injured limb generated lower average eccentric flexor torque towards the outer range of motion in comparison to the HG uninjured limb (P = 0.034) and the CG bilateral average (P = 0.025). Furthermore, the EMG root mean square (RMS) decrease from the start to the end range of the eccentric flexor contraction was greater for the HG injured limb hamstrings than the CG bilateral average. During the transition from double- to single-leg stance, the EMG onsets of the HG injured limb (biceps femoris [BF] P < 0.001, medial hamstrings [MH] P = 0.001), and the HG uninjured limb (BF P = 0.023, MH P = 0.011) were earlier in comparison to the CG bilateral average. The transition normalised EMG RMS was significantly higher for the HG injured side BF (P = 0.032), MH (P = 0.039) and vastus lateralis (VL, P = 0.037) in comparison to the CG bilateral average. During the forward lunge, no significant differences were observed within- and between-groups for the normalised EMG amplitude prior to and following initial foot contact. These results suggest that during maximal isokinetic eccentric flexor contractions, the average torque and EMG activity is decreased towards the lengthened position of the hamstring-injured limb. This may be due to structural changes or neurophysiological inhibitory mechanisms. During the static weight bearing task an earlier onset of the HG hamstring muscles was evident in comparison to controls. The hamstrings and the VL of the injured limbs were activated at greater normalised amplitude. The increased muscle activation in the hamstring-injured limbs during the support phase may indicate a greater demand towards stability of the kinetic chain or changes in proprioceptive function. Future research should consider the mechanisms and clinical implications underlying a loss of eccentric flexor torque towards the outer range of contraction, and investigate why increased activation of thigh muscles occurs during the static weight bearing task in hamstring-injured athletes.
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29

Fong, Sitt Wai. "The effects of transforming growth factor-β2 on synaptic transmission at the mammalian neuromuscular junctions." Thesis, University of Aberdeen, 2009. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=133996.

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Transforming growth factor-βs (TGF-βs) are highly expressed in neural development but why the adult nervous system continues to express them is unclear. TGF-β2 is concentrated at mature neuromuscular junctions (NMJs) of mammalian skeletal muscle fibres, and the nerve terminal expresses TβR-II receptors. To test the role of TGF-β2 at mammalian NMJs, I performed four experiments. The first study tested whether TGF-β2 acutely modulates synaptic transmission at mature mammalian NMJs. Second, I asked if chronically reduced TGF-β2 expression disrupts synaptic transmission. Third, I asked if TGF-β2’s effects differ in terminals adapted to different activity patterns in vivo. Lastly, I asked whether TGF-β1, a related peptide to TGF-β2, is distinct in terms of its effects on transmitter release. Using single electrode potential recording, I found TGF-β2 significantly increased the amplitude of spontaneous released single neurotransmitter vesicles (miniature endplate potentials, MEPPs) and nerve stimulation evoked multi-vesicular release (endplate potentials, EPPs). These effects were blocked by L-vesamicol, a vesicular acetylcholine transporter inhibitor, and bafilomycin, a proton pump inhibitor, suggesting the increase in MEPP/EPP amplitude is due to increased vesicle filling presynaptically. These effects were also blocked by the MARK inhibitors, UO126 and PD98059, suggesting TGF-β2 acts via a MARK-dependent pathway. Postsynaptically, two electrode recording showed postsynaptic potential amplitude was enhanced by an increased fibre input resistance, suggesting TGF-β2 also acts postsynaptically. TGF-β2 reduced the number of vesicles released per stimulus (quanta content, QC) but this was blocked by atropine, showing this was indirect through autoreceptor negative feedback. Voltage clamp recording showed TGF-β2 significantly increased the miniature end plate currents (MEPCs), but not the end-plate currents (EPCs), supporting my initial hypothesis that TGF-β2 acts mainly presynaptically to increase vesicle filling. In TGF-β2+/- mice, I found greater MEPP amplitude variability. This supports my previous findings that TGF-β2 modulates vesicle filling. Unexpectedly, there was an excess in larger MEPP sizes (>0.88 mV), perhaps reflecting upregulation of either presynaptic signalling or another synaptic mediator. Two MEPP amplitude populations were induced in TGF-β2-treated TGF-β2+/- mouse NMJs, similar to the bimodal vesicle population in electroplaques. The extensor digitorum longus (EDL, ~95% fast fibres) and soleus (SOL, ~95% slow fibres) were used to investigate whether the TGF-β2-mediated effect differed between fibre types. Overall, TGF-β2 increased the quantal size (MEPP amplitude) in NMJs of both muscles, suggesting this effect is not fibre-type specific and, together with results in mice, that the TGF-β2-mediated increase in vesicle filling is common to all mammalian neuromuscular terminals. With respect to EPP amplitude and QC, the results differed between muscles. In EDL, the EPP amplitude was not significantly changed, whereas it increased in SOL. In EDL, QC was reduced but not in SOL. These difference compared to diaphragm perhaps do reflect muscle fibre-type dependent differences. TGF-β1, at 0.1 ng/ml, significantly reduced quantal size – the opposite of TGF-β2 at any concentration. One explanation would be that a receptor inhibition by TGF-β1 at low concentration interferes with endogenous TGF-β2 binding/receptor activation at the NMJ. However, when the TGF-β1 concentration was raised to 1 ng/ml, like TGF-β2, it significantly increased MEPP amplitude. This suggests that perhaps sufficient binding of TGF-β1 results in the receptor activation of TGF-β2 like signalling. Overall, I conclude that TGF-β2 enhances the size of spontaneous synaptic potentials in all types of muscle fibres, and this is much more rapid (1 hr vs 1 day) than at central neurone synapses in culture. Detailed study in the rat diaphragm shows it increased the evoked EPP amplitude, reduced QC and increased postsynaptic input resistance. Together, TGF-β2 would therefore enhance the postsynaptic depolarisation increasing synaptic strength, and by reducing QC, increase the efficiency of neurotransmission at mammalian NMJs. While unimportant for single stimuli in healthy terminals, by conserving vesicle use, it may help maintain release during stimulus trains, especially during neuromuscular disease.
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Chan, Chung-yan Tommy, and 陳頌恩. "Interconnections between the hand and face representations in the human motor system." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31970369.

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Chan, Chung-yan Tommy. "Interconnections between the hand and face representations in the human motor system." Hong Kong : University of Hong Kong, 2002. http://sunzi.lib.hku.hk/hkuto/record.jsp?B25100683.

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Ban, Joanne. "Novel Effects of the MuSK System in Muscles of Wild-Type and mdx Mice." Thesis, The University of Sydney, 2018. http://hdl.handle.net/2123/18704.

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The agrin/Muscle specific kinase (MuSK)/Rapsyn is the most established signalling pathway promoting the development of the neuromuscular junction. Duchenne muscular dystrophy (DMD) is an X-linked degenerative muscle disorder caused by complete loss of dystrophin protein from muscle sarcolemma and destabilisation of dystrophin associated protein complex (DAPC). A recent study reported reduced MuSK expression in the muscle of (dystrophin-deficient) mdx mouse and suggested that this might contribute to the dystrophic phenotype. In this thesis, AAV-MuSK/Rapsyn-GFP was injected into the tibialis anterior muscle of mdx mice to investigate the effects of elevating expression of MuSK or Rapsyn. Short term (3 weeks) overexpression of MuSK or rapsyn partially protected muscles of 8 week old mdx mice against acute eccentric contraction (EC)-induced loss of force. Immunofluorescence analysis showed higher level of β-dystroglycan (β-DG) intensity at the sarcolemma of MuSK overexpressed dystrophic muscle. In addition, the total β-DG protein was markedly elevated in MuSK overexpressed muscle homogenates (Chapter 3). β-DG is known to be a core DAPC that prevents EC-induced loss force, thus the restoration of β-DG may help to explain how MuSK protects dystrophic muscle from EC-induced loss of force. Early injection of AAV-MuSK-GFP into muscles of 3-4 weeks old mdx mice leads to significant reduction muscle mass at 12 weeks, resulting in an increase in specific force production compared to the control muscle. MuSK also caused a modest, but significant, reduction of the percentage of centrally nucleated myofibre (Chapter 4). Another key effect of overexpressing MuSK was a decay of nerve-evoked force during each tetanus. The loss of force increased progressively with the duration of the nerve stimulation train (100 or 150Hz) at 400, 800,1600ms. No decay of force was observed when the same muscle was stimulated directly, ruling out the possibility of muscle fatigue (Chapter 5). These results suggest that overexpressing MuSK can reduce the capacity for neuromuscular transmission, a possible negative-feedback function for MuSK. Together, these findings suggest the additional roles of MuSK in regulating neuromuscular transmission and protecting the extrasynaptic sarcolemma of muscle fibres in mdx mice.
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Machado, Flavia Costa Nunes. "Análise do jitter com agulha concêntrica em pacientes com miastenia gravis autoimune adquirida." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/5/5138/tde-22082016-145446/.

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INTRODUÇÃO: A técnica de eletromiografia de fibra única (EMGFU), mediante análise do jitter, é o método neurofisiológico mais sensível para a confirmação do distúrbio da junção neuromuscular na miastenia gravis (MG). Os registros são tradicionalmente obtidos com agulha de fibra única, de alto custo e reutilizável. Por causa da necessidade atual do uso de material descartável, a agulha concêntrica vem sendo utilizada em substituição à agulha de fibra única. A técnica utilizada é semelhante, porém os potencias de ação para a análise do jitter são obtidos com eletrodo de agulha concêntrica (Eletromiografia de fibra única - jitter com agulha concêntrica, EMGFU-JAC). Contudo, os estudos são escassos e as metodologias utilizadas são heterogêneas com a utilização dessa agulha. OBJETIVOS: Este estudo tem por objetivo mensurar os valores de jitter obtidos com agulha concêntrica, no músculo Orbicularis Oculi, em sujeitos saudáveis e em pacientes com MG autoimune adquirida e avaliar a validade do método nas formas generalizada e ocular da doença. MÉTODOS: Foram estudados 20 sujeitos saudáveis, 20 pacientes com miastenia gravis forma generalizada (grupo MGG) e 13 com a forma ocular da doença (grupo MGO). A EMGFU-JAC foi realizada em todos os participantes, idealmente com 20 medidas de jitter em cada estudo. O jitter foi expresso como a média das diferenças consecutivas (MCD). Em todos os pacientes do estudo foram realizados o teste de estimulação repetitiva e dosagem sérica de anticorpo antirreceptor de acetilcolina (ac-AChR) no momento da análise do jitter. Nos pacientes soronegativos para ac-AChR, foi pesquisado o anticorpo antimúsculo específico tirosina-quinase (ac-MuSK). Foram definidos o limite superior da normalidade (LSN) para a média do MCD de cada estudo e para valores individuais de MCD. Os critérios de anormalidade foram: (1) média do MCD acima do LSN; ou (2) mais de 10% dos valores individuais de MCD acima do LSN. A definição do LSN para valores individuais de MCD baseou-se no conceito de que dois entre 20 valores de MCD acima do LSN são aceitáveis em um músculo saudável, para a técnica de contração voluntária. Portanto, estimou-se o LSN para o 18o valor mais alto de MCD (18o par). Para análise da acurácia do método, foram construídas duas curvas ROC (Receiver Operating Characteristic) para as variáveis média do MCD e 18o par, no grupo de pacientes (MGG e MGO) versus controle. RESULTADOS: No grupo controle a média das médias do MCD foi (19,0 ± 2,4)us e a média do 18o valor mais alto de cada estudo foi (24,5 ± 3,6)us. Esses valores obtidos apresentaram distribuição Gaussiana e o LSN foi definido como a média desses valores + 2 DP. O LSN para a média do MCD foi 24us, e 32?s para valores individuais de MCD. No grupo MGG, a análise do jitter foi anormal em todos os 20 pacientes por ambos os critérios de anormalidade, exceto em um paciente que apresentou anormalidade por apenas um dos critérios. No grupo MGO, apenas um dos 13 pacientes não preencheu os critérios de anormalidade. No grupo de pacientes, a positividade da EMGFU-JAC foi maior do que o teste de estimulação repetitiva e dosagens de anticorpos. Nas curvas ROC para as variáveis médias do MCD e 18o par, o valor de melhor sensibilidade (93,9%), sem resultados falsos positivos, foi 24,7us e 33,1us, respectivamente. CONCLUSÕES: A EMGFU-JAC apresenta alta sensibilidade e especificidade na identificação de distúrbio da transmissão neuromuscular em pacientes com MG. A utilização da agulha concêntrica é válida para a análise do jitter, como alternativa à agulha de fibra única
INTRODUCTION: Single fiber electromyography (SFEMG) technique, through jitter analysis, is the most sensitive neurophysiological method for confirmation of neuromuscular junction disorder in myasthenia gravis (MG). Records are traditionally obtained with single fiber needle, which is reusable and has a high-cost. Due to the current need of using disposable material, concentric needle has been used to replace single fiber needle. The technique is similar, but the action potential for jitter analysis is obtained with concentric needle electrode (SFEMG - concentric needle jitter, SFEMG-CNJ). However, studies are scarce and methodologies used are heterogeneous with the use of this needle. OBJECTIVES: This study aims to measure jitter values obtained with concentric needle in the Orbicularis Occuli muscle in healthy subjects and in patients with autoimmune acquired MG and to assess the validity of the method in generalized and ocular forms of the disease. METHODS: 20 healthy subjects, 20 patients with generalized myasthenia gravis (GMG group) and 13 with the ocular form of the disease (OMG group) were studied. SFEMG-CNJ was performed on all participants, ideally with 20 jitter values in each study. Jitter was expressed as the mean consecutive difference (MCD). Repetitive nerve stimulation and serum acetylcholine receptor antibody (AChR-ab) were performed in all patients in the study, by the time of jitter analysis. Tyrosine kinase specific antibody muscle antibodies (MuSK-ab) were performed in AChR-ab negative patients. The upper limit of normality (ULN) for the mean MCD and for individual jitter values were defined. The abnormality criteria were: (1) mean MCD above ULN; or (2) more than 10% of individual jitter values above ULN. The definition of ULN for individual jitter values was based on the concept that two out of 20 jitter values above ULN are acceptable in a healthy muscle for voluntary contraction technique. Therefore, the ULN for the 18th highest jitter value (18 pair) was estimated. To analyze the method\'s accuracy, two ROC curves (Receiver Operating Characteristic) for the mean MCD and 18th pair in the group of patients (MGG and MGO) versus control were constructed. RESULTS: In the control group the mean of MCD means was (19.0 ± 2.4)us and the mean of the 18 highest value of each study was (24.5 ± 3.6)us. These values showed Gaussian distribution and the ULN was set as the mean of these values + 2 SD. The ULN for the mean MCD was 24us, and 32us for individual values of MCD. In GMG group, jitter analyses were abnormal in all 20 patients based on both abnormality criteria, except in one patient, who had abnormalities in only one of the criteria. In OMG group, only one patient from 13 met neither of the abnormality criteria. In patients, the positivity of SFEMG-CNJ was higher than repetitive nerve stimulation test and antibody detection. The ROC curve threshold showing the best sensitivity (93.9%) with no false positive results was 24.7Us for the mean MCD and 33.1us for individual pairs, respectively. CONCLUSIONS: SFEMG-CNJ has high sensitivity and specificity in identifying neuromuscular transmission disorder in patients with MG. The use of concentric needle is valid for jitter analysis as an alternative to single fiber needle
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Giovannini, Federica. "Voltage-dependent calcium channel subtypes at the mouse neuromuscular junction : evidence for the role of a resistant component." Thesis, University of Oxford, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.365445.

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Panchumarthi, Sarvari. "The Drosophila Serrate is Required for Synaptic Structure and Function at Larval Neuromuscular Junctions." Diss., The University of Arizona, 2010. http://hdl.handle.net/10150/194269.

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Drosophila melanogaster is an excellent model system to identify genes involved in synaptic growth and function. In Drosophila, the Serrate (Ser) gene encodes a transmembrane protein that is a ligand for Notch receptor. Several previous studies implicated a role for Serrate in normal wing development and patterning. In this study, I demonstrate that Serrate is required for normal synaptic growth and function. I characterized the phenotype of a Serrate mutation (serB936) that was identified by an EMS-induced genetic screen aimed at identifying novel genes that play a role in synaptic growth and function. Co-localization studies show that Serrate protein is expressed at both the pre- and postsynaptic side of larval neuromuscular junctions (NMJs). Mutations in ser impair synaptic transmission at larval NMJs. This defect is entirely presynaptic, as nerve-evoked excitatory junction potentials (EJP) and quantal content (QC) of neurotransmitter release are significantly reduced when compared to wild-type control. Further, mutations in ser also alter the growth of the NMJ and the underlying muscle. Mutations in ser significantly reduce the size of larval body wall muscles (length and surface area) as well as the number and size of synaptic boutons, and the number of secondary axonal branches. Ubiquitous or muscle-specific expression of normal Serrate in serB936 mutants restores a normal muscle size but not a normal size and structure of the innervating NMJ. However, expression of normal Serrate in the motor axon restores a normal number of synaptic boutons and secondary branches at serB936 mutant NMJs. In addition, it restores normal neurotransmitter release. These data suggest that Serrate protein is required presynaptically for normal synaptic growth and function. Interestingly, overexpression of Serrate in a wild type background resulted in similar phenotypes than to those of loss-of-function mutants. In conclusion, these data suggest a new functional role for Serrate in synaptic growth and function.
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Jonsson, Malin. "Nicotinic transmission and drugs in anesthesia : neuromuscular blocking agents and propofol : consequences for carotid body function /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-660-3/.

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MacLennan, Calman Alexander. "Acetylcholine receptor subunit gene expression in different muscle groups and the thymus : a study of healthy subjects and of those with disordered neuromuscular transmission." Thesis, University of Oxford, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390531.

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Caudron, Audrey. "Molecular changes following genetic and physical disruption of neuromuscular synapses in developing and adult mice /." [St. Lucia, Qld.], 2006. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe19325.pdf.

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Sittaramane, Vinoth Chandrasekhar Anand. "Role of transmembrane protein strabismus in motor neuron migration in the zebrafish hindbrain." Diss., Columbia, Mo. : University of Missouri--Columbia, 2008. http://hdl.handle.net/10355/6623.

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Title from PDF of title page (University of Missouri--Columbia, viewed on Feb 25, 2010). The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Dissertation advisor: Dr. Anand Chandrasekhar. Vita. Includes bibliographical references.
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Mendez, Villanueva Alberto. "Mechanical power output and neuromuscular activity during and following recovery from repeated-sprint exercise in man." University of Western Australia. School of Human Movement and Exercise Science, 2005. http://theses.library.uwa.edu.au/adt-WU2005.0055.

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The purpose of the present study was to examine the time-course of mechanical power output and neuromuscular activity during fatiguing repeated-sprint exercise and recovery in man. Prior to the main study, we also investigated the reproducibility of power output during a single 6-s cycling sprint. For this study, eleven healthy moderately trained males performed a 6-s standing sprint on the front-access cycle ergometer on four separate occasions. The results of the study showed that reliable power outputs can be obtained after one familiarization session in subjects unfamiliar with maximal cycling sprint exercise. However, the inclusion of an extra familiarization session ensured more stable power outputs. Therefore, two trials should allow adequate familiarization with the maximal 6-s cycling test. For the main study, eight young moderately trained adult men performed an exercise protocol that consisted of ten, 6-s sprints on a wind-braked cycle ergometer interspersed with 30 s of recovery. After 6 min of passive recovery, five, 6-s sprints were repeated, again interspersed by 30 s of recovery. Peak power output (PPO) and mean power output (MPO) were measured during each sprint and EMG data (i.e., RMS) from the vastus lateralis muscle were also recorded. A one-way ANOVA with repeated measures (i.e., sprint number) was used to allocate the significant differences in each dependent variable over time. Analysis revealed a decline in power output during the fatiguing exercise that was accompanied by a decrease in EMG amplitude of the vastus lateralis muscle. Six minutes after the fatiguing exercise, power output during sprint 11 significantly recovered with respect to values recorded in sprint 10, but remained significantly lower than that recorded in the initial sprint. Thus, 6 min was insufficient to fully recover from the fatiguing repeated sprint protocol utilised in this study. The main findings in the present study were that: 1) the partial recovery of power output in sprint 11 was not accompanied by the recovery V of EMG amplitude; 2) similar mean power outputs were recorded during sprint 4 and 11 despite a significantly lower EMG activity recorded during the latter sprint; and 3) despite comparable mean power outputs during sprint 4 and 11, the decrease in power output over the next five sprints was greater for sprints 11 to 15 than for sprints 4 to 8.
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Bruneteau, Gaëlle. "Etude de la jonction neuromusculaire dans la sclérose latérale amyotrophique." Thesis, Paris 6, 2014. http://www.theses.fr/2014PA066097/document.

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La Sclérose Latérale Amyotrophique (SLA) est une affection neurodégénérative touchant les motoneurones, habituellement mortelle en 3 à 5 ans. La cause de la maladie n'est pas connue et le seul traitement actuellement disponible ne permet qu'un allongement modeste de la survie. Des altérations fonctionnelles de la jonction neuromusculaire (JNM) ont été rapportées dans la SLA mais leur origine physiopathologique n'est pas connue. Nous avons étudié les JNM chez 11 patients atteints de SLA, en associant étude morphologique en microscopie confocale et analyse ultrastructurale. L'analyse fonctionnelle réalisée en EMG de surface retrouvait une anomalie de transmission neuromusculaire (décrément > 10%) chez 45% des patients. Des altérations morphologiques des JNM étaient visibles chez tous les patients, y compris au stade précoce de la maladie. Associé aux anomalies en rapport avec le phénomène de dénervation, nous avons observé un aspect anormal de spiculation de la gouttière primaire dans environ un tiers des cas. Une interposition marquée de la cellule de Schwann terminale entre la terminaison nerveuse et la membrane postsynaptique, pouvant altérer la transmission synaptique, était parfois visible. Nous avons objectivé une réinnervation compensatrice significativement plus importante chez les patients présentant une SLA d'évolution lente et montré que certains facteurs moléculaires musculaires comme l'histone déacétylase 4 pourraient jouer un rôle crucial dans la capacité de réinnervation. Ce travail a mis en évidence des altérations morphologiques majeures au niveau des JNM des patients atteints de SLA et a permis d'identifier des cibles thérapeutiques potentielles
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder affecting motor neurons, usually leading to death in 3 to 5 years. The only treatment currently available, riluzole, has a modest effect on survival. Functional alterations of the neuromuscular junction (NMJ) have been reported in ALS, but their pathophysiological significance remains unknown. We studied the morphology of neuromuscular junctions in muscle samples collected from 11 ALS patients, using confocal and electron microscopy. Functional analysis of the NMJs was performed using surface-recording of compound motor action potentials after repetitive nerve stimulation at slow stimulus rate. A significant decrement (>10%), suggesting impairment of the neuromuscular transmission, was present in 45% of the patients. Morphological alterations of the NMJs were present in all ALS patients even at the early-stages. Beside denervation-induced morphological changes, one third of the NMJs showed abnormal spike-like areas of the outer edge of the postsynaptic primary gutter. A marked interposition of the terminal Schwann cell between the nerve terminal and the postsynaptic membrane, which was likely to alter synaptic transmission, was sometimes present. We found a significantly greater compensatory reinnervation in muscle from patients with slowly progressive ALS. Furthermore, we identified that the muscle molecular factor histone deacetylase 4 could play a key role in muscle reinnervation and disease progression in patients with ALS. This work has highlighted the presence of major morphological changes at the NMJs of ALS patients and identified potential new targets for future treatment
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Halliez, Marius. "Le domaine riche en cystéine de MuSK dans la myasthénie auto-immune." Electronic Thesis or Diss., Sorbonne université, 2023. http://www.theses.fr/2023SORUS093.

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La synapse périphérique établie entre la terminaison d'un axone moteur et une fibre musculaire striée squelettique est appelée jonction neuromusculaire (JNM). La formation, la maturation ainsi que la maintenance de la JNM sont des processus finement régulés dans le temps et l'espace. L'ensemble de ces phénomènes nécessite une communication dynamique entre les différents compartiments cellulaires qui composent la JNM. La rupture totale ou partielle de ces signalisations trans-synaptiques mène à des altérations morpho-fonctionnelles de la JNM à l'origine des pathologies neuromusculaires. Ces maladies graves, parmi lesquelles, les syndromes myasthéniques congénitaux ou la myasthénie grave (MG), impactent fortement les fonctions motrices et menacent la vie des patients. Même si les outils de diagnostic de ces pathologies sont bien connus, la compréhension des mécanismes moléculaires et cellulaires impactés est encore incomplète et les traitements disponibles limités. Afin de mettre au point de nouvelles stratégies thérapeutiques, il est nécessaire de mieux caractériser les signalisations impliquées dans la connectivité neuromusculaire. L'ensemble des étapes de mise en place de la JNM nécessite la présence et l'activité d'un complexe de récepteurs clés ancrés dans la membrane musculaire. Il est composé du récepteur à activité tyrosine kinase MuSK (Muscle Specific Kinase) et de son co-récepteur Lrp4 (Low density lipoprotein receptor-related 4). Ce complexe est activé par plusieurs ligands parmi lesquels, l'Agrine libérée par la terminaison motoneuronale ainsi que les glycoprotéines Wnt. De cette activation découle l'agrégation des récepteurs à l'acétylcholine (RACh) dans la zone synaptique de la cellule musculaire, un phénomène caractéristique de la différenciation post-synaptique. Les précédents travaux réalisés par l'équipe ont permis de mettre en évidence l'implication d'un réseau de signalisations Wnt à la JNM, notamment médiées par le domaine riche en cystéines (CRD) de MuSK correspondant au domaine de liaison des Wnt. Même si l'étude des animaux chez lesquels le CRD de MuSK est absent (MuSKΔCRD) a révélé des défauts morphologiques et fonctionnels importants de la JNM, cette mutation ne menace pas la survie des animaux contrairement à la délétion de Lrp4, de MuSK ou de l'Agrine. La MG est une maladie auto-immune causée par la présence d'anticorps qui ciblent, dans 85% des cas, le RACh. On retrouve dans une faible proportion de patients, des anticorps dirigés contre MuSK, ciblant habituellement le domaine Ig1 impliqué dans la signalisation Agrine. Cependant, trois études ont mis en évidence la présence d'anticorps se liant spécifiquement au CRD de MuSK chez des patients atteints de MG sans que l'on sache si ces anticorps sont pathogéniques et capables d'induire la maladie. La caractérisation de ces anticorps et la démonstration de leur potentiel pathogène représente donc un élément important dans la compréhension des mécanismes physiopathologiques sous-jacents de la myasthénie. Dans ce contexte, mes travaux de thèse ont porté sur la démonstration de la pathogénicité des anticorps anti-CRD de MuSK. Mes résultats ont montré que l'injection d'anticorps ciblant le CRD de MuSK mène à l'apparition d'un phénotype myasthénique chez la souris. Via un large éventail d'expériences de biologie cellulaire, biochimie et d'électrophysiologie, j'ai montré que les symptômes cliniques étaient accompagnés de graves défauts de structure de la JNM et de neurotransmission. Sur le plan mécanistique, mes travaux ont prouvé que la présence de ces anticorps mène à la rupture de l'interaction entre Lrp4 et MuSK inhibant ainsi l'agrégation des RACh induite par l'Agrine. L'ensemble de cette étude permet de mettre en évidence une nouvelle signalisation impactée dans un contexte de MG, de mieux comprendre la pathogénicité du CRD de MuSK et participe à l'adaptation des traitements alloués aux patients en fonction de leur étiologie
The peripheral synapse established between the end terminal of a motor neuron and a skeletal muscle fiber is the neuromuscular junction (NMJ). Formation, maturation and maintenance of the NMJ are finely tuned in time and space. These processes require a dynamic communication between all the cellular compartments of the NMJ. Total or partial disruption of this trans-synaptic signaling result in morpho-functional defects responsible for neuromuscular disorders. These pathologies, including the congenital myasthenic syndromes and the auto-immune myasthenia gravis (MG), deeply impact motor function in patients and threaten their life. Even though diagnostic tools are well established, the cellular and molecular mechanisms are yet poorly understood and available treatments are limited. In order to develop new promising therapeutic strategies, it is critical to better characterize all the signaling pathways involved in neuromuscular connectivity. NMJ formation relies on the presence and activity of a complex of key receptors anchored in the muscle membrane. This complex is composed of the tyrosine kinase receptor MuSK (Muscle Specific Kinase) and its co-receptor Lrp4 (Low density lipoprotein receptor-related 4) and is activated by different ligands including the nerve-derived Agrin and Wnt glycoproteins. Activation of this complex leads to acetylcholine receptor (AChR) clustering in the muscle synaptic area, a hallmark of post-synaptic differentiation. Previous studies from our group showed the implication of a network of Wnt pathways at the NMJ, partly signaling through the Wnt-binding cysteine rich domain (CRD) of MuSK. Even if mouse model in which MuSK is deleted from its CRD (MuSKΔCRD) display important morphological and functional defects, this mutation is compatible with life as opposed to Lrp4, MuSK or Agrin deletion. MG is an auto-immune disorder caused by antibodies targeting, in 85% of cases, the AChR. A small percentage of patient harbor antibodies against MuSK, usually against its Ig1 domain, involved in Agrin signaling. Three recent studies revealed MG patients carrying MuSK CRD targeting antibodies but whether these antibodies are pathogenic remains unknown. Characterization of their pathogenicity remains crucial to better understand the pathophysiological mechanisms leading to MG. In this context, my thesis work aims at demonstrating the pathogenicity of CRD MuSK antibodies. My results showed that injection of antibodies targeting MuSK CRD leads to a myasthenic-like phenotype in mouse. Using a large array of cell biology, biochemistry and electrophysiological experiments, I showed that the clinical symptoms were accompanied by important structural and neurotransmission defects at the NMJ. Mechanistically, my work proved that antibodies against MuSK CRD are responsible for Lrp4-MuSK interaction disruption ultimately leading to inhibition of Agrin-induced AChR clustering. Altogether, this study unravels a new pathway affected in MG, participates to a better understanding of MuSK CRD implication in this pathology and helps treatment adaptation regarding patients etiology
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Bingham, Stephanie. "Cellular and molecular analysis of motor neuron development in the zebrafish hindbrain /." free to MU campus, to others for purchase, 2003. http://wwwlib.umi.com/cr/mo/fullcit?p3115523.

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44

Zhu, Yuechen. "THE EFFECT OF COLD ON THE PHYSIOLOGY OF DROSOPHILA LARVA HEART AND ON SYNAPTIC TRANSMISSION AT CRAYFISH NEUROMUSCULAR JUNCTIONS." UKnowledge, 2017. http://uknowledge.uky.edu/biology_etds/50.

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Ectothermic animals are susceptible to temperature changes such as cold shock with seasons. To survive through a cold shock, ectotherms have developed unique strategies. My interest is focusing on the physiological function of during cold shock and prolonged cold exposure in the fruit fly (Drosophila melanogaster) and crayfish (Procambarus clarkii). I used Drosophila melanogaster as a model system to investigate cardiac function in response to modulators (serotonin, acetylcholine, octopamine, dopamine and a cocktail of modulators) in acute cold shock and chronic cold shock conditions as possible mechanism to regulate heart rate in the cold. To examine if the dampened heart rate in the cold could still be enhanced by modulators or calcium loading, modulators and light-sensitive channelrhodopsin proteins were utilized to stimulate the heart. This light induced cardiac activation increased heart rate in all conditions, and potentially can be used for cardiac therapy in mammals. Also, the acute and chronic cold conditioned heart showed responsiveness to the above mention modulators. In examining how synaptic transmission is influenced by acute and chronic cold, the crayfish neuromuscular junction was used as a model. This is a good model as there are high and low output synapses to be investigated. The low output neuromuscular junction was enhanced in response to acute cold. The high output nmj increased in synaptic response to acute cold. In addressing chronic cold conditions, the nmj were physiologically assayed in their response to acute warm changes as well as influence of serotonin and octopamine. In chronic cold condition, the synaptic output was varied in enhanced and dampened responses to an acute warm environment. These junctions were enhanced in their synaptic output by serotonin and octopamine (100nM). In assessing, by HPLC assay, octopamine concentration increased in chronic cold crayfish. This suggests compensation in synaptic transmission in cold acclimation possibility via endocrine responses.
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45

Vitry, Florian. "Effets aigus et chroniques de l’électrostimulation appliquée au niveau du nerf moteur : importance du retour afférent." Thesis, Bourgogne Franche-Comté, 2019. http://www.theses.fr/2019UBFCK087.

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L'objectif de cette thèse était d’étudier l'impact de protocoles d’électrostimulation favorisant un recrutement indirect des unités motrices (UM) via les afférences sensorielles et induisant le développement d’extra force, sur le système neuromusculaire. Ces protocoles associent une grande largeur d’impulsion, une faible intensité de stimulation, des hautes et basses fréquences et sont appliqués sur le nerf moteur. L’étude des effets de ces protocoles sur la fatigue neuromusculaire lors d’une application aiguë a fait l’objet de la première étude qui a montré que pour un impact équivalent sur la capacité maximale de production de force, les basses fréquences de stimulation limitaient la diminution de force au cours d’une session d’électrostimulation comparativement aux hautes fréquences. L’application de manière chronique de ces protocoles lors d’un entraînement a fait l’objet de la deuxième étude. Les résultats ont montré des gains de force importants malgré les faibles intensités de stimulation et des adaptations nerveuses qui étaient dépendantes de la fréquence de stimulation. Les résultats de ces deux études ont aussi permis de mettre en évidence l’importance du phénomène d’extra force sur les adaptations induites. Ainsi, l’étude de ce dernier phénomène a fait l’objet de la troisième étude. Les résultats ont montré que lorsque le recrutement initial des UM était indirect, l’extra force était présente pour toutes les fréquences de stimulation. De plus, le développement de l'extra force a induit une diminution de l’excitabilité spinale après les basses fréquences de stimulation et une augmentation après les hautes fréquences. La dernière étude de ce travail s’est intéressée aux mécanismes expliquant ces modulations spinales. Les résultats ont montré que le mécanisme de dépression post-activation pourrait expliquer la diminution observée après les basses fréquences, tandis que ce mécanisme serait compensé par la présence de courants entrants persistants, entraînant une augmentation de l’excitabilité des motoneurones après les hautes fréquences de stimulation. L’ensemble de ces résultats souligne l’importance du retour afférent aux adaptations neuromusculaires induites après une application aiguë et chronique de l’électrostimulation
The aim of this thesis was to investigate the effects of electrical stimulation protocols favouring an indirect motor units’ (MU) recruitment via sensory axons activation and giving rise to extra force development, on the neuromuscular system. These protocols use wide pulse duration, low stimulation intensity, low and high stimulation frequencies and are applied over the motor nerve. The aim of the first study was to examine the effects of these protocols on the extent and origin of neuromuscular fatigue during an acute application. Results showed that for a similar impact on maximal force generating capacity, low stimulation frequencies limit force decreases during the stimulation trains as compared to high stimulation frequencies. The aim of the second study was to investigate the effects of chronic application of these protocols. Results showed important torque gains after the training period despite the low stimulation intensity used, while the induced neural adaptations were frequency-dependent. Results of these two studies also highlighted the importance of the phenomenon of extra torque on induced adaptations. Thus, the aim of the third study was to determine the conditions permitting the occurrence of extra torque, by modulating the frequency and intensity of stimulation. Main results showed that when the initial MU recruitment was mostly indirect, the developed torque was higher than the one expected for the given stimulation parameters, independently of the stimulation frequency, suggesting that the indirect MU recruitment plays a preponderant role in the occurrence of extra torque. Moreover, a frequency-dependent impact on spinal excitability was observed, resulting in a decrease after the low stimulation frequency and an increase after the high frequency. Consequently, the last study investigated the mechanisms responsible for the distinct modulation of spinal excitability. Results showed that the decrease in spinal excitability observed after the low stimulation frequency could be attributed to increased homosynaptic post-activation depression, while this latter mechanism could have been compensated by an enhanced motoneuron excitability as a result of persistent inward currents after the high stimulation frequency. All these results underline the importance of the afferent volley to the induced neuromuscular adaptations after acute and chronic electrical stimulation application
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46

Munhoz, Derli Conceição 1964. "Influencia da frequencia de estimulos sobre o bloqueio neuromuscular produzido pelo pancuronio e pelo rocuronio : um estudo clinico e experimental." [s.n.], 2003. http://repositorio.unicamp.br/jspui/handle/REPOSIP/313571.

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Orientadores: Angelica de F. Assunção Braga, Gloria M. Braga Poterio
Tese (doutorado) - Universidade Estadual de Campínas, Faculdade de Ciencias Medicas
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Resumo: Além dos fatores relacionados ao paciente, ao bloqueador neuromuscular, fatores técnicos relacionados com a monitorização da função neuromuscular podem influenciara instalação do bloqueio neuromuscular. O objetivo do presente estudo foi avaliar a influência de duas diferentes freqüências de estúnulos sobre o tempo de instalação do bloqueio neuromuscular produzido pelo Pancurônio e pelo Rocurônio. Este estudo foi desenvolvidoem duas etapas: uma etapa clínica e uma experimental. No estudo clínico foram incluídos 120 pacientes, estado ASA I e lI, submetidos a cirurgias eletivas sob anestesia geral, distn"buídos aleatoriamente em dois grupos de acordo com a freqüência de estúnulos empregada: Grupo I - O,lHz (n=60) e Grupo II - 1Hz (n=60). Em cada grupo formaram-se dois subgrupos (n=30) de acordo com o bloqueador neuromuscular empregado: Subgrupo P (pancurônio - O,lmg.kg-l) e Subgrupo R (rocurônio - 0,6mg.kgO1). Após indução anestésica e injeção do bloqueador neuromuscular, os pacientes foram ventilados sob máscara com oxigênio a 100% até a obtenção de redução de 75% ou mais na amplitude da resposta do músculo adutor do polegar, quando foram realizadas as manobras de laringoscopia e intubação traqueal. A função neuromuscular foi monitorizada com aceleromiografia. Avaliaram-se: parâmetros neuromusculares (tempo de início de ação do bloqueador neuromuscular e tempo para bloqueio neuromuscular total) através da análise dos registros das respostas do músculo adutor do polegar obtidas por estimulação do nervo ulnar, com auxílio de estimulador de nervo periférico (TOF-GUARD); condições de intubação traqueal; pressão arterial média e fteqüência cardíaca. No grupo 1,subgrupos P e R, os tempos para início de ação foram, respectivamente, 159,33 :t 35,22 e 83,0 :t 17,25 segundos. No grupo lI, subgrupos P e R, foram 77,83 :t 9,52 e 48,96 :t 10,16 segundos, respectivamente. Os tempos para obtenção de bloqueio neuromuscular total foram 222,0 :t 46,56 e 125,33 :t 20,12, no Grupo 1,subgrupos P e R, respectivamente.No grupo lI, foram de 105,96:t 18,58 e 59,83 :t 10,36 segundos nos subgrupos P e R respectivamente. Nos dois subgrupos, os tempos de início de ação e para bloqueio neuromuscular total foram significativamente menores no Grupo II em relação ao Grupo I. As condições de intubação traqueal foram satisfatórias em 117 pacientes (97,5%) e insatisfatórias em 3 (2,5%). No estudo experimental foram utilizados ratos machos da linhagem Wistar, com peso entre 250 e 300g. As preparações foram montadas de acordo com a técnica descrita por BULBRING (1946). O diafTagma foi submetido à estimulação indireta de 0,1 e 1Hz de :freqüência (Grupos I e II, respectivamente) e as variações de tensão produzidas pelas contrações do diaftagma foram registradas em fisiógrafo Gould RS 3400. Formaram-se subgrupos (n=5) PE e RE de acordo com o bloqueador neuromuscular empregado (pancurônio-2J.1g/rnle rocurônio-4J.1g/rnl,respectivamente). O grau de bloqueio das respostas do músculo diaftagma foi avaliado em 5, 15 e 30 minutos após a adição do bloqueador neuromuscular. Nos dois grupos (Grupo I - O,lHz e Grupo II - 1Hz) e subgrupos PE (pancurônio) e RE (rocurônio), observou-se um aumento cumulativo nos graus de bloqueio das respostas musculares com diferença significativa entre os diferentes tempos estudados em relação à resposta muscular controle. Nos dois subgrupos, a comparação dos valores médios dos graus de bloqueio nos diferentes tempos estudados entre os dois grupos também mostrou diferença estatisticamente significante. Para as duas drogas, os graus de bloqueio neuromuscular para o Grupo II foram maiores do que para o Grupo I, em todos os instantes (p < 0,01). Concluímos que, tanto no estudo clínico como no experimenta~ a freqüência de estímulo empregada interfere no tempo de instalação do bloqueio neuromuscular: tempo de início de ação e de bloqueio neuromuscular total menores com a maior freqüência nos dois subgrupos
Abstract: In addition to factors related to patient and neuromuscular blocker, technical factors related to neuromuscular monitoring may also influencethe onset of neuromuscular blockade. The aim of the present study was to evaluate the influence of two different stimulation :&equencieson onset time of the neuromuscular blockade produced by Pancuronium and Rocuronium. This study was conducted in two stages: clinical and experimental. The clinical study included 120 patients, ASA I and II physical status, submitted to elective surgery under general anesthesia, random1y distributed into two groups according to the stimulation :&equencyused: GToup 1-0.1 Hz (n=60) and GToup lI-I Hz (n=60). In each group two subgroups were formed (n=30), according to the neuromuscular blocker used: Subgroup P (pancuronium-O.l mg.kg-l) and Subgroup R (rocuronium-0.6 mg.kg-l). Afier induction of anesthesia and injection of the neuromuscular blocker, the patients were ventilated by mask with 100% oxygen until achieving a 75% or more reduction in the amplitude of the abductor pollicis muscle response. That was the moment laryngoscopy and tracheal intubation were performed. Neuromuscular function was monitored by acceleromyography. Neuromuscular parameters were evaluated (the onset time of NMB action and time to maxima1 neuromuscular blockade) ana1yzingrecordings of adductorpollicis muscle response, obtained by stimulating the ulnar nerve with a neuromuscular transmission monitor (TOF-GUARD). Tracheal intubating conditions, mean arterialpressure and heart rate were also evaluated. In GToupI, onset times for subgroups P and R were 159.33 :i:35.22and 83.0 :i: 17.25 seconds, respectively. In GTouplI, onset times for subgroups P and R were 77.83 :i:9.52 and 48.96 :i: 10.16 seconds, respectively. Times to maxima1neuromuscularblockadein GToupI, subgroupsP and R were 222.0 :f: 46.56 and 125.33 :f: 20.12 seconds, respectively. In GTouplI, times to maxima1neuromuscular blockwere 105.96 :i: 15.58 and 59.83 :i: 10.36 for subgroups P and R, respectively. In both subgroups, onset times of action and times to maxima1 neuromuscular block were significant1yshorter in GToup II than in GToup I. Tracheal intubating conditions were suitable in 117 (97.5%) and unsuitable in 3 (2.5%) patients. In the experimental study, Wistar male rats, weighing between 250 and 300g were used. Microscope preparation was mounted according to the technique described by BULBRING (1946). An indirect stimulation of 0.1 to 1 Hz was applied to the diaphragm (GToupsI and lI, respectively) and tension variations produced by diaphragmatic contractions were recorded by a Gould RS 3400 physiographer. Subgroups PE and RA (n=5) were fonned, according to the neuromuscular blocker used (pancuronium-2 ~g/m1and rocuronium-4 ~g/m1,respective1y). The degree of diaphragmatic blockade was evaluated at 5, 15 and 30 minutes after adding the neuromuscular bIocker. In both groups (Group 1-0.1 Hz and Group 11-1 Hz) and subgroups RE (rocuronium) and PE (pancuronium), a cumulative increase in the degree of musc1eblockade was observed. There was a significant difrerence between difrerent times studied compared to controI musc1e response. In both subgroups, there was also a statistica11ysignificant difrerence when comparing the mean values of degrees of bIockade between both groups at difrerent times studied. For both drugs, the degree ofneuromuscular bIock for Group 11is greater than for Group I, at alI moments (p<0.01). We conc1ude that both in the clinical and experimental study the stimulation ftequency applied interfere with the onset time of neuromuscularbIockade
Doutorado
Medicina Interna
Doutor em Ciências Médicas
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47

Patra, Kalicharan. "Modulation of Neuronal Functions : the Role of SLC10A4." Doctoral thesis, Uppsala universitet, Genetisk utvecklingsbiologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-214162.

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Mental health of a person depends on the correct functioning of the brain. The brain and the spinal cord contain many types of cells, of which one important type are called the neurons. Neurons are special in the way they connect to each other to form large networks. The chemicals called transmitters are packed at the nerve endings into tiny packets called vesicles and when a signal arrives these vesicles fuse immediately to the attached cell surface and release their contents. The role of the synaptic vesicular transporter proteins is to ensure proper packing of transmitter molecules that can be released upon stimulation. Vesicular packing is an important process. The carrier proteins involved in packing work in coordination to determine the amount and type of transmitters to be packed. Missing a carrier protein from the vesicles might lead to improper packing and inaccurate signaliing. These signaling molecules are known for their implications in many psychiatric and neurological disorders like Alzheimer’s disease, Parkinson’s disease, Schizophrenia, and attention deficit to name just a few.  How a vesicular transporter can affect the modulatory functions of aminergic neurons is the subject of this thesis. This thesis reports on the effects of the loss of a vesicular orphan transporter. Study I demonstrates the localization of this protein to monoaminergic and cholinergic terminals. It reports the effect of the loss of Slc10A4 on vesicular dopamine uptake, synaptic clearance of dopamine and hypersensitivity of animals to dopamine related psychostimulants. Study I also provides evidence for ATP as a possible ligand for SLC10A4 protein. Study II provides data on the clinical relevance of Slc10A4 in playing a protective role against vulnerability to epilepsy. It reports that loss of Slc10A4 renders the animals hypersensitive to cholinergic drugs. Study III provides a closer look at individual cholinergic synapses at neuromuscular junctions in mice lacking Slc10A4. The structural and electrophysiological properties of the NMJ are found compromised because of the loss of this vesicular protein. Taken together, this thesis presents a SV protein’s perspective of viewing at modulation of synaptic transmission.
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48

Megeath, Laura Jalso. "Characterization of the Molecular Mechanisms Regulating the Agrin Signaling Pathway: a Dissertation." eScholarship@UMMS, 1999. https://escholarship.umassmed.edu/gsbs_diss/29.

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The nervous system requires rapid, efficient, and accurate transmission between cells for proper functioning. Synapses are the predominant structures through which such vital communication occurs. How synapses are formed, maintained, and eliminated are questions of fundamental importance. At the nerve-muscle synapse, formation of the postsynaptic apparatus is directed by agrin. The hallmark activity of agrin is the aggregation of acetylcholine receptors (AChRs) into dense clusters opposite the presynaptic nerve terminal. Early events in the agrin signal transduction cascade include activation of the receptor tyrosine kinase MuSK and tyrosine phosphorylation of AChRs, but how these events lead to AChR cluster formation is unknown. Using the calcium buffer BAPTA, we demonstrate that intracellular calcium fluxes are necessary for agrin-induced formation of AChR clusters. However, clamping calcium fluxes before agrin stimulation does not alter agrin-induced phosphorylation of either MuSK or AChRs, indicating that this calcium-dependent step occurs downstream of both MuSK and AChR phosphorylation. These results identify a new step in the agrin signaling pathway required for the formation of AChR clusters. We show that intracellular calcium fluxes also play an important role in stabilizing AChR clusters. Clamping intracellular calcium fluxes results in rapid dispersal of AChR clusters and dephosphorylation of both MuSK and AChRs, even if agrin is continually present. Furthermore, the protein tyrosine phosphatase inhibitor pervanadate inhibits both the dispersal and dephosphorylation, indicating a role for a tyrosine phosphatase in AChR cluster dispersal. Our data indicate that AChR clusters are maintained by agrin/MuSK-induced intracellular calcium fluxes that tonically inhibit a tyrosine phosphatase localized to AChR clusters. Our findings also show that distinct molecular mechanisms mediate the formation and the dispersal of agrin-induced AChR clusters. The work presented here expands our understanding of synaptic differentiation in several ways. First, I characterized a new, calcium-dependent step required for the formation of agrin-induced AChR clusters. Next, I showed that postsynaptic specializations must be actively maintained, and describe a molecular mechanism that stabilizes AChR clusters. Finally, dispersal and formation of AChR clusters occurs by distinct pathways. Our understanding of the mechanisms regulating the formation and modulation of synapses will help us to better understand how the nervous system develops and responds to the world around us.
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49

Fuentes, Medel Yuly F. "Role of Glia in Sculpting Synaptic Connections at the Drosophila Neuromuscular Junction: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/580.

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Emerging evidence in both vertebrates and invertebrates is redefining glia as active players in the development and integrity of the nervous system. The formation of functional neuronal circuits requires the precise addition of new synapses. Mounting evidence implicates glial function in synapse remodeling and formation. However, the precise molecular mechanisms governing these functions are poorly understood. My thesis work begins to define the molecular mechanisms by which glia communicate with neurons at the Drosophila neuromuscular junction (NMJ). During development glia play a critical role in remodeling neuronal circuits in the CNS. In order to understand how glia remodel synapses, I manipulated a key component of the glial engulfment machinery, Draper. I found that during normal NMJ growth presynaptic boutons constantly shed membranes or debris. However, a loss of Draper resulted in an accumulation of debris and ghost boutons, which inhibited synaptic growth. I found that glia use the Draper pathway to engulf these excess membranes to sculpt synapses. Surprisingly, I found that muscle cells function as phagocytic cells as well by eliminating immature synaptic ghost boutons. This demonstrates that the combined efforts of glia and muscle are required for the addition of synapses and proper growth. My work establishes that glia play a crucial role in synapse development at the NMJ and suggests that there are other glial-derived molecules that regulate synapse function. I identified one glial derived molecule critical for the development of the NMJ, a TGF-β ligand called Maverick. Presynaptically, Maverick regulates the activation of BMP pathway confirmed by reducing the transcription of the known target gene Trio. Postsynaptically, it regulates the transcription of Glass bottom boat (Gbb) in the muscle suggesting that glia modulate the function of Gbb and consequently the activation of the BMP retrograde pathway at NMJ. Surprisingly, I also found that glial Maverick regulates the transcription of Shaker potassium channel, suggesting that glia potentially could regulate muscle excitability and consequently modulate synaptic transmission. Future work will elucidate such hypothesis. My work has demonstrated two novel roles for glia at the NMJ. First is that glia engulfing activity is important for proper synaptic growth. Second is that the secretion of glial-derived molecules are required to orchestrate synaptic development. This further supports that glia are critical active players in maintaining a functional nervous system.
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50

Sohn, Mark Hongchul. "Assessing functional stability of predicted muscle activation patterns for postural control using a neuromechanical model of the cat hindlimb." Thesis, Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/42869.

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The underlying principles of how the nervous system selects specific muscle activation pattern, among many that produce the same movement, remain unknown. Experimental studies suggest that the nervous system may use fixed groups of muscles, referred to as muscle synergies, to produce functional motor outputs relevant to the task. In contrast, predictions from biomechanical models suggest that minimizing muscular effort may be the criteria how a muscle coordination pattern is organized for muscle synergies. However, both experimental and modeling evidence shows that stability, as well as energetic efficiency, also needs to be considered. Based on the hypothesis that the nervous system uses functionally stable muscle activation pattern for a muscle synergy, we investigated the stability of muscle patterns using a neuromechanical model of the cat hindlimb. Five unique muscle patterns that generate each of the five experimentally-identified muscle synergy force vectors at the endpoint were found using a minimum-effort criterion. We subjected the model to various perturbed conditions and evaluated functional stability of each of the five minimum-effort muscle synergies using a set of empirical criteria derived from experimental observations. Results show that minimum-effort muscle synergies can be functionally stable or unstable, suggesting that minimum-effort criterion is not always sufficient to predict physiologically relevant postural muscle synergies. Also, linearized system characteristics can robustly predict the behavior exhibited by fully dynamic and nonlinear biomechanical simulations. We conclude that functional stability, which assesses stability of a biomechanical system in a physiological context, must be considered when choosing a muscle activation pattern for a given motor task.
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