Дисертації з теми "Neuromuscular development"
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-50 дисертацій для дослідження на тему "Neuromuscular development".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте дисертації для різних дисциплін та оформлюйте правильно вашу бібліографію.
Ribchester, Richard R. "Development and plasticity of neuromuscular innervation." Thesis, University of Edinburgh, 2005. http://hdl.handle.net/1842/29963.
Повний текст джерелаLee, Chi Wai. "Development of the presynaptic nerve terminal during neuromuscular synaptogenesis /." View abstract or full-text, 2005. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202005%20LEE.
Повний текст джерелаCurrie, Douglas A. "Neuromuscular development in the adult abdomen of Drosophila melanogaster." Thesis, University of Cambridge, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239201.
Повний текст джерелаBenatar, Michael G. "Presynaptic function in development and disease at the neuromuscular junction." Thesis, University of Oxford, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388959.
Повний текст джерелаTeriakidis, Adrianna. "Intra-neuronal influences on development of the mammalian neuromuscular junction." Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/25245.
Повний текст джерелаBroadie, Kendal Scot. "Development of the neuromuscular junction in the embryo of Drosophila melanogaster." Thesis, University of Cambridge, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309336.
Повний текст джерелаLandgraf, Matthias. "Mechanisms underlying the development of neuromuscular connectivity in the Drosophila embryo." Thesis, University of Cambridge, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627075.
Повний текст джерелаPujari, Amit Narahar. "Development and evaluation of vibration apparatus and method for neuromuscular stimulation." Thesis, University of Aberdeen, 2016. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=231217.
Повний текст джерелаCôté, Patrice D. "Dystroglycan function in development and neuromuscular disease : a study by gene targeting." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=36900.
Повний текст джерелаClark, 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.
Повний текст джерелаZhou, Jie. "Functions of tyrosine kinases and phosphatases in presynaptic development during neuromuscular junction formation /." View abstract or full-text, 2007. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202007%20ZHOU.
Повний текст джерелаTelfer, Scott. "The development of a novel adaptive seating system for children with neuromuscular disorders." Thesis, University of Strathclyde, 2011. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=15486.
Повний текст джерелаSugimoto, Daisuke. "ANTERIOR CRUCIATE LIGAMENT PREVENTION: EFFECT OF NEUROMUSCULAR TRAINING COMPLIANCE ON MUSCULAR STRENGTH DEVELOPMENT." UKnowledge, 2013. http://uknowledge.uky.edu/rehabsci_etds/22.
Повний текст джерелаQian, Yueping. "The roles of protein tyrosine phosphatases in the development of the neuromuscular junction /." View abstract or full-text, 2008. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202008%20QIAN.
Повний текст джерелаHuber, Alexander. "Tissue Engineering of Neuromuscular Junctions, Development of An Alternative to The LD50 Toxicity Test." Thesis, University of Nottingham, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.485014.
Повний текст джерелаRoss, A. J. "Multiple roles of integrin-α3 in the development and maintenance of the neuromuscular junction". Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1471753/.
Повний текст джерелаLi, Yihang. "Mechanisms of Synaptic Development and Premature Aging in Drosophila: A Dissertation." eScholarship@UMMS, 2009. http://escholarship.umassmed.edu/gsbs_diss/862.
Повний текст джерелаUzel, Sébastien G. M. "Microfluidic and optogenetic technologies to model spinal cord development and neuromuscular junction formation and function." Thesis, Massachusetts Institute of Technology, 2015. http://hdl.handle.net/1721.1/103850.
Повний текст джерела"June 2015." Cataloged from PDF version of thesis.
Includes bibliographical references (pages 106-118).
Motor neurons located in the spinal cord and innervating muscle cells throughout the body are responsible for virtually all motor functions, from locomotion to respiration or speech. They arise from differentiation of progenitor cells within the neural tube under spatiotemporally well-defined morphogen concentration profiles, and extend axons into the peripheral nervous system following a precisely orchestrated sequence of events involving secreted chemo-attractants and repellents and dynamic expression of the corresponding ligand receptors. Finally, they form neuromuscular junctions, the synapses that transmit electrical signals to the muscle effectors. Failure for these motor neurons to develop or function properly, caused by developmental or neurodegenerative genetic disorders, or as a result of traumatic injuries, lead to highly incapacitating or even lethal malformation and conditions. Microfabricated platforms and optogenetic technologies have proven to be valuable tools to control the microenvironment, biochemical cues and the stimulation applied to neuronal tissues. Precise control of the geometry of microfluidic devices together with their ability to host 3D cell culture has enhanced the physiological relevance of such neuronal tissues relative to traditional 2D culture assays. And the ability to selectively excite neuronal cells with light has opened tremendous opportunities in the field of neuroscience. In this thesis, we combine these two technologies to stimulate and subject cells to chemical and physical microenvironments that emulate their in vivo counterpart. First, we present a microfluidic platform that generates orthogonal concentration gradients and emulates the confined appearance of motor neurons within the developing spinal cord. Then, we introduce a new device capable of forming a 3D compartmentalized neuron-muscle coculture and demonstrate remote stimulation of the myofibers by the motor neurons resulting in muscle contraction. By targeting the stem cells from which the motor neurons are derived with the light sensitive ion channel Channelrhodopsin, we form, in this microfluidic device, the first in vitro light-activatable neuromuscular junction. Keywords: microfluidics, optogenetics, morphogenesis, cell migration, neuromuscular junctions.
by Sébastien G. M. Uzel.
Ph. D.
Schafer, Carol Linda. "Development of a functional neuromuscular stimulation (FNS) muscle training program to prepare paraplegics for standing." Master's thesis, University of Cape Town, 1989. http://hdl.handle.net/11427/25845.
Повний текст джерелаJokhi, Vahbiz. "Synapse Development: Ribonucleoprotein Transport from the Nucleus to the Synapse: A Dissertation." eScholarship@UMMS, 2016. https://escholarship.umassmed.edu/gsbs_diss/853.
Повний текст джерелаVincent, Kelly Anne. "The development and validation of a patient-centred quality-of life questionnaire for adult neuromuscular disease." Thesis, King's College London (University of London), 2003. https://kclpure.kcl.ac.uk/portal/en/theses/the-development-and-validation-of-a-patientcentred-qualityof-life-questionnaire-for-adult-neuromuscular-disease(2344fbff-c701-4369-8a5b-76395bbafd4f).html.
Повний текст джерелаBingham, 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.
Повний текст джерелаStocksley, Mark Alan. "Neural control of the distribution of voltage-gated sodium channels during development of the rat neuromuscular junction." Thesis, University of Newcastle Upon Tyne, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.324797.
Повний текст джерелаLi, Yihang. "Mechanisms of Synaptic Development and Premature Aging in Drosophila: A Dissertation." eScholarship@UMMS, 2016. https://escholarship.umassmed.edu/gsbs_diss/862.
Повний текст джерелаRoche, Sarah Louise. "Importance of axon-glial interactions for the normal postnatal development of the mouse peripheral nervous system." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/15888.
Повний текст джерелаMusi, Wennergren Alexander. "Neuromuscular electrical stimulation after anterior cruciate ligament reconstruction surgery : Effects on rate of torque development and electromechanical delay." Thesis, Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:gih:diva-3773.
Повний текст джерелаAbstrakt Syfte: Huvudsyftet med denna studie var att jämföra elektromekaniska fördröjning (EMD) och vridmoment utveckling (RTD) för knäextensorerna 6 veckor efter rehabilitering av främre korsbandsrekonstruktion (ACLR) med eller utan neuromuskulär elektrisk stimulering (NMES). Vidare undersöktes genomförbarheten av studien. Metod: 10 deltagare randomiseras in i två grupper, en neuromuskulär elektrisk stimulerings grupp (NMESG) och en träningsgrupp (TG). NMESG använde en NMES - enhet som ett komplement till ordinarie rehabiliteringsprotokoll. Regelbundna möten med sjukgymnast var inplanerad under rehabiliteringen. Mätningar av RTD och EMD under knäets extension gjordes i en isokinetisk dynamometer med elektromyografi inspelningar (EMG) från knäextensorerna 6 veckor efter operationen. Resultat: Alla deltagare fullföljde studien. NMESG träffade sjukgymnasten 6,7 ± 2,5 gånger och TG 6,8 ± 1,8 gånger. Deltagarna i NMESG använde NMES - apparaten 28 ± 1,7 gånger. Totalt antal träningsdagar för NMESG var 25 ± 4 och för TG 35 ± 1. RTD skiljde sig inte signifikant mellan grupperna. För TG var RDT 901,1, 941,2 och 531,0 Nm/s, under de respektive första 50, 100 och 200 ms. För NMESG var RTD 824,3, 966,2 och 529,0 Nm/s, under de respektive första 50, 100 och 200 ms. Inga signifikanta skillnader mellan grupperna eller samspel mellan grupp och muskler hittades i EMD. För båda grupperna var EMD signifikant större för vastus medialis jämfört vastus lateralis och rectus femoris. Slutsats: Studien var möjligt att utföra, och trots färre träningsdagar för NMESG sågs inga signifikanta skillnader mellan grupperna i RTD eller EMD. Det behövs en större studiepopulation för att utvärdera effekten av interventionen.
Ruas, Cassio V. "Neuromuscular characteristics of eccentric contractions of the knee extensors and their muscle damage profiles." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2021. https://ro.ecu.edu.au/theses/2437.
Повний текст джерелаTavoian, Dallin. "Tools and Technologies for Assessing, and Exercise Strategies for Promoting, Neuromuscular Function and Mobility in Aging." Ohio University / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1615816378173099.
Повний текст джерелаKuhn, Camila. "Estudo morfológico do músculo extensor longo dos dedos da prole de ratas obesas submetidas ou não à cirurgia de derivação gástrica em Y de Roux." Universidade Estadual do Oeste do Paraná, 2018. http://tede.unioeste.br/handle/tede/4166.
Повний текст джерелаMade available in DSpace on 2019-03-29T16:57:16Z (GMT). No. of bitstreams: 2 Camila_Kuhn2018.pdf: 2657327 bytes, checksum: 9eb518e6dcb5d576b52f1606ea47d2fa (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-04-03
Studies show that maternal obesity can affect fetal development, resulting in diseases in adult life, such as diabetes mellitus type 2, cardiovascular disease, obesity itslef. To reduce the effects of obesity and its comorbidities, bariatric surgeries stand out among the most effective interventions, with Roux-en-Y gastric bypass (RYGB) being the most frequently performed type of bariatric procedure. However, there are still few studies in the literature that evaluate the effects of obesity and bariatric surgeries on the morphology of skeletal muscle tissue in adult offspring. Thus, the objective of this study was to evaluate microscopic parameters of muscle fibers and neuromuscular junctions (NMJs) of the extensor digitorum longus muscle (EDL) in obese rats’ offspring submitted or not to RYGB surgery. Three-week Wistar rats were randomly divided into three groups: Control Group (CTL) which received a standard diet; 2) Cafeteria False Operated (CAF FO) and 3) Cafeteria RYGB (CAF RYGB), the latter two received a cafeteria diet before and after the surgical procedure until the weaning of the offspring. In the 18th of life, the surgical procedure and false operation were performed in the CAF RYGB and CAF FO groups, respectively. The mating of the animals occurred five weeks after the surgical procedure. The birth of the offspring was postnatal day 0, and weaning occurred at three weeks of age, and only the male offspring were separated for the experiment. The offspring of the first generation (F1) were named CTL-F1, OB-F1, CAF FO-F1 and CAF RYGB and received standard diet. At 17 weeks the animals were euthanized and the EDL muscle collected for analysis of fiber muscles and NMJs. When the CTL-F1 and OB-F1 groups were analyzed, the latter had an increase in body weight, retroperitoneal and periepididymal fats, and capillary/fiber ratio. Reduction in the number of nuclei, conjunctive and morphological changes in the parameters evaluated in the ultrastructure. The area and larger diameter of NMJs also showed reduction. The analysis between CAF RYGB-F1 and CAF FO-F1 groups showed reduction of body weight, ELD muscle weight, retroperitoneal and periepididimal fat, nasoanal length, fiber area and nuclei/fiber ratio in the CAF RYGB-F1 group. This group also presented increase in the number of fibers of type I and IIa and number of capillaries, as well as reduction in the area of the NMJs and morphological alterations in the ultrastructure. These results demonstrate that both obesity and bariatric surgery expose the offspring, through metabolic programming, to effects on the morphology of skeletal muscle tissue, being found greater aggravations in the muscular fiber of the offspring of mothers submitted to RYGB.
Estudos apontam que a obesidade materna pode afetar o desenvolvimento fetal, resultando em doenças na vida adulta, tais como diabetes mellitus tipo 2, doenças cardiovasculares e a própria obesidade. Para reduzir os efeitos da obesidade e as suas comorbidades, as cirurgias bariátricas destacam-se entre as intervenções mais eficazes, sendo a derivação gástrica em Y de Roux (DGYR) o tipo de procedimento bariátrico mais frequentemente realizado. No entanto, ainda são escassos na literatura estudos que avaliem os efeitos da obesidade e das cirurgias bariátricas na morfologia do tecido muscular esquelético da prole adulta. Diante disso, o objetivo deste estudo foi avaliar a morfologia e a morfometria das fibras musculares e as junções neuromusculares (JNMs) do músculo extensor longo dos dedos (ELD) da prole de ratas obesas submetidas ou não à cirurgia de DGYR. Para tanto, ratas Wistar de três semanas de vida foram separadas aleatoriamente em três grupos: 1) Controle (CTL), que recebeu dieta padrão; 2) Cafeteria Falso operado (CAF FO) e 3) Cafeteria DGYR (CAF DGYR); esses dois últimos receberam dieta de cafeteria antes e após o procedimento cirúrgico, até o desmame da prole. Na 18ª semana de vida, foi realizado o procedimento cirúrgico e a falsa operação nos grupos CAF DGYR e CAF FO, respectivamente. O cruzamento dos animais ocorreu cinco semanas após o procedimento cirúrgico. O nascimento dos animais foi considerado o dia zero pós-natal e o desmame se deu na terceira semana vida, quando somente os machos foram separados para o experimento. A prole da primeira geração (F1) foi nomeada em CTL-F1, OB-F1, CAF FO-F1 e CAF DGYR-F1 e todos os animais receberam dieta padrão. Na 17ª semana, os animais foram eutanasiados e o músculo ELD coletado para análise das fibras musculares e JNMs. Quando analisado os grupos CTL-F1 e OB-F1, esse último apresentou aumento do peso corpóreo, das gorduras retroperitoneal e periepididimal, e relação capilar/fibra. Além disso, houve a redução do número de núcleos, conjuntivo e alterações morfológica nos parâmetros avaliados na ultraestrutura. A área e diâmetro maior das JNMs também apresentaram redução. A análise entre os grupos CAF DGYR-F1 e CAF FO-F1 evidenciou redução do peso corporal, do peso do músculo ELD, da gordura retroperitoneal e periepididimal, don comprimento nasoanal, da área das fibras e relação núcleo/fibra no grupo CAF DGYR-F1. Esse grupo também apresentou aumento no número de fibras do tipo I e IIa e no número de capilares, assim como redução na área das JNMs e alterações morfológicas na ultraestrutura. Esses resultados demonstram que tanto a obesidade como a cirurgia bariátrica expõem a prole, por meio da programação metabólica, com efeitos na morfologia do tecido muscular esquelético, sendo encontrado maiores agravos na fibra muscular da prole de mães submetidas à DGYR.
Murray, David Vernon. "The effect of maximal isometric training on doublet-induced force enhancement and its relationship with changes in voluntary rate of force development." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2018. https://ro.ecu.edu.au/theses/2074.
Повний текст джерелаPinto, Stephanie Santana. "Efeitos de um treinamento concorrente na hidroginástica sobre as variáveis neuromusculares e cardiorrespiratórias de mulheres jovens e pós-menopáusicas." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2013. http://hdl.handle.net/10183/72455.
Повний текст джерелаThe aim of the present study was to compare the effects of the intra-session exercise order (i.e., resistance-aerobic or aerobic-resistance) during water-based concurrent training on the neuromuscular and cardiorespiratory variables in young and postmenopausal women. Twenty-six young women (25.12 ± 2.94 years) were randomly assigned into two groups in study I: resistance-aerobic (RA) (n=13) and aerobicresistance (n=13). For study II, twenty-one postmenopausal women were also randomly assigned into two groups: resistance-aerobic (RA) (n=10) and aerobic-resistance (n=11). In both studies the subjects performed the water-based concurrent training two times a week during 12 weeks, performing both resistance and aerobic training in the same session. The resistance training was performed with sets at maximal effort and the aerobic training with exercises at heart rate corresponding to the second ventilatory threshold. All variables were evaluated before and after training. A repeated measure ANOVA with group factor was used to analyze the data of the present study (α=0.05). After training in study I, with the young women, there was a significant increase in the maximal dynamic strength in all muscle groups (elbow and knee flexors and extensors) evaluated using the one-repetition maximal test (1RM). The RA group presented grater relative gains of the knee extensors maximal dynamic strength compared to the AR group (43.58 ± 14.00% vs. 27.01 ± 18.05%, respectively). After training there was a significant increase of the maximal isometric peak torque (PT) of all muscle groups (except elbow extensor PT) evaluated using the Biodex dynamometer, with no difference between RA and AR groups. In addition, after training there was a significant increase of the maximal rate of force development (RFD) and of the RFD at different windows (50, 100, 250 ms) during the knee extension maximal isometric voluntary contraction (MIVC), with no difference between RA and AR groups. There was a significant increase of the maximal isometric electromyography (EMG) activity of biceps brachii and vastus lateralis after training, with no difference between RA and AR groups. Moreover, the submaximal isometric EMG activity of biceps braachi at 40% of MIVC, the submaximal isometric EMG activity of vastus lateralis at 40% and 80% of MIVC and the submaximal isometric EMG activity of rectus femoris at 80% of MIVC showed lower values after training, with no difference between RA and AR groups. After training, there was a significant increase of the muscle thickness of biceps brachii, brachialis, vastus medialis and rectus femoris, with no difference between RA and AR groups. The relative gains of the muscle thickness of the vastus lateralis and vastus intermedius were greater for the RA group compared to the AR group (vastus lateralis: 10.00 ± 7.64% vs. 5.28 ± 3.42%, vastus intermedius: 11.58 ± 5.36% vs. 4.40 ± 3.77%, respectively). The height of the countermovement jump improved after training, with no difference between RA and AR groups. In addition, the peak oxygen uptake (VO2peak) and corresponding to the first ventilatory threshold (VO2VT1) showed significant increases after training, with no difference between RA and AR groups. In study II, with the postmenopausal women, there was a significant increase in the maximal dynamic strength of the elbow flexors and extensors, with no difference between RA and AR groups. The knee extensors 1RM in the RA group showed greater increases than the AR group (34.62 ± 13.51% vs. 14.16 ± 13.68%). After training, there were significant increases of the knee flexors and extensors PT, with no difference between RA and AR groups. In addition, there was a significant increase in the knee extension maximal RFD and in the knee extension RFD at different windows (50, 100, 250 ms), with no difference between RA and AR groups. Moreover, there were increases of the maximal isometric EMG activity of vastus lateralis and rectus femoris, with no difference between RA and AR groups. Furthermore, the submaximal isometric EMG activity of rectus femoris at 40% of MIVC showed lower values after training, with no difference between RA and AR groups. Also, there were significant increases of the muscle thickness of all muscles evaluated, with no difference between RA and AR groups (except rectus femoris). Significant increase was also observed in the oxygen uptake corresponding to the second ventilatory threshold (VO2VT2) after training, with no difference between RA and AR groups. In summary, the intra-session exercise order with resistance exercises prior to aerobic exercises optimizes the knee extensors maximal dynamic strength gains in young and postmenopausal women, as well as the quadriceps femoris muscle thickness in young women when compared to the inverse order (i.e., aerobic-resistance).
Schläger, Sarah Joanna [Verfasser], Jan St [Akademischer Betreuer] Kirschke, Jan St [Gutachter] Kirschke, Marcus [Gutachter] Deschauer, and Dimitrios [Gutachter] Karampinos. "Development and validation of MR-based quantitative biomarkers for detection of pathological changes in skeletal muscle tissue of patients with neuromuscular diseases / Sarah Joanna Schläger ; Gutachter: Jan St. Kirschke, Marcus Deschauer, Dimitrios Karampinos ; Betreuer: Jan St. Kirschke." München : Universitätsbibliothek der TU München, 2021. http://d-nb.info/1240832664/34.
Повний текст джерелаBonnin, Edith. "Elucidating the Functional Role of Human Nucleoporin Nup88 in Health and Disease." Doctoral thesis, Universite Libre de Bruxelles, 2018. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/268017.
Повний текст джерелаDoctorat en Sciences
info:eu-repo/semantics/nonPublished
Salga, Marjorie. "Inflammation et paraostéoarthropathies neurogènes Blocking neuromuscular junctions with botulinum toxin A injection enhances neurological heterotopic ossification development after spinal cord injury in mice Traumatism brain injury: if neurological damage was not the key to the development of neurogenic heterotopic ossification? Corticosteroid injection is an alternative therapeutic strategy to treat pain in Neurogenic Heterotopic Ossification: a Case Series." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLV072.
Повний текст джерелаHeterotopic ossifications (H0) are abnormal ectopic bone formations that develop in soft tissues. HO can be related to genetic factors or acquired pathologies. HO occurring after central nervous system lesion are called neurogenic HO (NHO). The objective of this project is to identify local and systemic inflammatory factors that may be associated with occurrence of NHO. We study first, the effect of bacterial membrane components on the development of NHO in a mouse model of spinal cord injury triggered by injection of a myotoxic compound into muscle. Local and systemic administration of membrane components from Escherichia coli or Staphylococcus aureus significantly increased the volume of NHO. Changes in the level of inflammation, which was dose responsive, correlated with changes in NHO volume suggesting that inflammation influences NHO formation. As bacterial membrane components were also linked to increased volumes of NHO, it is possible that inflammation triggered by infectious pathogens could also be involved in NHO development. Furthermore, we identified that after reaching a certain threshold of inflammation, triggered by administration of bacterial membrane components, spinal cord injury was not required for NHO formation. Further experiments with this model involved determining the effect of blocking neuromuscular signaling on NHO formation. Botulinum toxin injection increased the size of NHO. Therefore, neuromuscular signaling also modulates NHO development in damaged muscles of spinal cord-injured mice. By extension, local neuroinflammation was implicated in regulating neuromuscular signals received by affected muscles. Based on these preclinical results, we carried out a case-control study to look for factors inducing inflammation that could be linked with NHO occurrence, and which occur at early stages after neurological trauma. This study identifies for the first time that patients with Pseudomonas Aeruginosa-positive infections were more likely to develop NHO. NHO patients more frequently experience surgery and polytrauma, compared to patients without NHO. Furthermore, extended stays in intensive care, long periods of mechanical ventilation, enduring coma, or patients with a tracheotomy were more frequent in patient with NHO. In contrast, no neurological factors were associated with a higher risk of developing NHO. Patients with comparable neurological trauma severity were more susceptible to develop NHO when they were experiencing a high level of inflammation (infection, polytrauma, surgeries, intensive care). Like for other inflammatory joint pathologies, we performed a further study which involved the infiltration of NHO with corticosteroid locally, in order to treat pain induced by NHO formation. One month after treatment, 80% of patients reported an improvement of pain. Therefore, we demonstrate that corticosteroid infiltration at the site of NHO is an effective treatment for pain associated with NHO. Detecting patients that are at risk to develop NHO as early as possible after an accident is imperative, to adapt rehabilitative strategies or treatment needs specific for patients that develop NHO. However, NHO diagnosis occurs during late phase of disease, when complications are occurring. To address this shortfall in the detection of NHO formation, we are undertaking the first prospective study of NHO, where clinical and biological information will be recorded to make a database. The specific data to be collected has been defined by our previous research in the mouse model and earlier clinical studies, and will identify specific biological and clinical factors that can be monitored to identify patients at risk to develop NHO. The outcomes of this project have specific implications in the understanding the drivers of NHO formation and its detection. Global outcomes of this project include improving patient management and possibly the prevention of NHO formation in patients
Omerza, Frank F. "Neural plasticity in vertebrate metamorphosis : a developmental study of neuromuscular connectivity /." The Ohio State University, 1992. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487780865406536.
Повний текст джерелаNadal, Magriñà Laura. "Muscarinic, adenosine and tropomyosin-related kinase B receptors modulate the neuromuscular developmental synapse elimination process." Doctoral thesis, Universitat Rovira i Virgili, 2017. http://hdl.handle.net/10803/441749.
Повний текст джерелаEl desarrollo del sistema nervioso periférico implica una inicial exuberante producción de neuronas y, una posterior reducción dependiente de actividad del número de sinapsis en las uniones neuromusculares (NMJ). Este proceso se denomina eliminación sináptica. Al final de la segunda semana postnatal, cada fibra muscular esta inervadas por una solo motoneurona. Los receptores muscarínicos de acetilcolina (mAChR), los receptores de adenosina (AR) y el receptor quinasa de tropomiosina B (TrkB) podrían permitir la competición entre los terminales nerviosos durante el proceso de eliminación sináptica mediante la modulación en la liberación de acetilcolina. En esta tesis se ha investigado, mediante microscopía confocal y un análisis morfológico cuantitativo, el papel de los receptores mAChRs (M1, M2 y M4), de los receptores de adenosina (A1 y A2A) y del receptor TrkB en el del proceso de eliminación en el desarrollo de la NMJ. Los resultados muestran que los receptores mAChRs, AR y el receptor TrkB promueven una desconexión axonal al inicio de la segunda semana postnatal independientemente de la maduración de los receptores de acetilcolina postsinápticos. En resumen, los receptores mAChRs, AR y el receptor TrkB retrasan el proceso de eliminación sináptica en P7 pero lo aceleran en P9. En la cooperación de estos receptores, se ha demostrado que M4 produce un efecto oclusivo sobre M1 y aditivo sobre A1 en P7. La cooperación entre M1, A1 y A2A promueve la pérdida axonal en P9, mientras que M2 es independiente de los otros receptores. M1 y TrkB cooperan para incrementar la pérdida axonal en P9 independientemente de M2 y TrkB. En conclusión, la eliminación sináptica postnatal está regulada por un mecanismo que depende de varios receptores, involucrando la cooperación de diferentes subtipos de receptores muscarínicos, de adenosina y el receptor TrkB, los cuales garantizan la monoinnervación de las sinapsis neuromusculares al final del proceso. saludable.
The development of the peripheral nervous system involves an initially exuberant production of neurons and a subsequent activity-dependent reduction in the number of synapses at the neuromuscular junctions (NMJ). This process is called synaptic elimination. At the end of the first postnatal week, each muscle fiber is innervated by a single motoneuron. Muscarinic acetylcholine receptors (mAChR), adenosine receptors (AR) and the tropomyosin-related kinase B (TrkB) receptor may allow the direct competition between nerve endings during synapse elimination through the modulation of acetylcholine release. Here, it has been investigated by confocal microscopy and quantitative morphological analysis the involvement of the individual and synergic or oclusive effect of M1-, M2- and M4-subtypes of mAChRs, A1 and A2A of ARs and TrkB in the control of the axonal elimination in developing NMJ. The results show that mAChRs, ARs and TrkB promote axonal disconnection at the beginning of the second postnatal week without affecting the postsynaptic maturation of the nicotinic receptor cluster. In summary, mAChRs, ARs and TrkB delay axonal loss at P7 but accelerate it at P9. In terms of receptor cooperation, M4 produces some occlusion of the M1 pathway and some addition to the A1 pathway at P7. The cooperation between M1, A1 and A2A receptors promotes axonal loss at P9, whereas the effect of M2 is independent of the other receptors. M1 and TrkB receptors work together to increase axonal loss rate at P9 but the effect of M2 is largely independent of the TrkB receptor. In conclusion, postnatal synapse elimination is a regulated multireceptor mechanism involving the cooperation of several muscarinic, adenosine and TrkB receptor subtypes that guarantees the monoinnervation of the neuromuscular synapses in the end of the process.
Sharma, Nidhi. "Developmental expression analysis and RNA interference (RNAi) screen of putative neuromuscular receptors of «Schistosoma mansoni»." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=123300.
Повний текст джерелаEn plathelminthes parasites, y compris Schistosoma mansoni la coordination de système neuromusculaire est essentiel pour continuer à se propager, le développement et la réussite du cycle de vie. Signalisation neuromusculaire chez ces parasites est médiée par une variété de neurotransmetteurs, les petites molécules (classique) des émetteurs et des neuropeptides. Les amines biogènes (BA) constituent le plus grand sous-ensemble de neurotransmetteurs classiques et jouent plusieurs rôles clés dans le contrôle de la fonction musculaire schistosome et le mouvement. Il RNA ya plusieurs récepteurs BA putatifs identifiés dans le génome de S. mansoni, dont la majorité sont des récepteurs couplés aux protéines de classe AG (GPCR). Nous rapportons ici le rôle fonctionnel de ces récepteurs putatifs de BA dans le développement du parasite et de la motilité par analyse de l'expression du développement et de dépistage RNAi. Nous avons effectué une analyse de l'expression de plusieurs récepteurs de BA putatifs au niveau de l' dans les différents stades de développement du parasite, en utilisant la transcription inverse couplée à une PCR quantitative (RT- qPCR). Une de ces protéines est un récepteur de la sérotonine décrit précédemment de S. mansoni (nommé Sm5HTR) et les autres sont de nouveaux récepteurs "orphelins" BA -like . L'analyse a montré que les récepteurs de la BA testés sont exprimés dans tous les stades de développement mais la majorité sont préférentiellement exprimé dans les cercaires et schistosomule, suggérant que ces récepteurs jouent un rôle particulièrement important dans les larves de parasite. Suivant nous avons effectué l'interférence RNA (RNAi) de cibler les mêmes récepteurs de BA par transfection larves S.mansoni avec petits RNA interférents (siRNA) et analysé les effets sur l'activité motrice par comparaison avec les groupes témoins. Étant donné que le BAs sont des modulateurs du mouvement schistosome connu, nous avons supposé que l' RNAi serait de produire un phénotype de moteur dans les larves et cela a été confirmé par les données. Les résultats identifiés phénotypes fortement hypoactif pour trois des quatre récepteurs testés, y compris Sm5HTR (Smp_126730), Smp_150180 et Smp_120620), tous montrant une réduction significative de mouvement par rapport à lutter contre les larves transfectées avec non pertinentes (brouillés) siRNA. Le phénotype RNAi corrélée avec un effet de choc important et spécifique dans les niveaux de transcription tel que déterminé par RT- qPCR. Pour élucider le mode d'action de Sm5HTR nous avons également effectué une analyse de immunolocalisation confocale en utilisant un anticorps anti- peptide spécifique. Le profil d'expression suggère Sm5HTR est très abondant dans le système nerveux central et périphérique du parasite, y compris l'innervation périphérique des muscles de la paroi du corps chargés de mouvement. Ensemble, les résultats suggèrent que Sm5HTR et d'autres récepteurs de la BA jouent un rôle important dans le contrôle de la motilité schistosome, en particulier les larves, et pourraient être des cibles potentielles pour la découverte de nouveaux médicaments.
Morgan-Jones, Melanie. "Does Fascia Bowen therapy improve neuromuscular function and psychological well-being in males aged 8-11 (at primary school) with dyspraxia/developmental coordination disorder?" Thesis, University of Bath, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.665409.
Повний текст джерелаJames, Rebecca E. "Crimpy Sorts a BMP into the Regulated Secretory Pathway for Activity-Dependent Release in Drosophila Motorneurons." Case Western Reserve University School of Graduate Studies / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=case1364994680.
Повний текст джерелаMota, Carla Patrícia Nunes da. "Development of a Stimulator for Neuromuscular Blockage Assessment." Master's thesis, 2018. https://repositorio-aberto.up.pt/handle/10216/113828.
Повний текст джерелаMota, Carla Patrícia Nunes da. "Development of a Stimulator for Neuromuscular Blockage Assessment." Dissertação, 2018. https://repositorio-aberto.up.pt/handle/10216/113828.
Повний текст джерелаMohseni, Paria. "Role of Nestin in Mouse Development." Thesis, 2010. http://hdl.handle.net/1807/32184.
Повний текст джерелаBennett, Alexis. "The role of RNA helicases in neuromuscular development and diseases." Thesis, 2016. https://hdl.handle.net/2144/16799.
Повний текст джерелаWang, Man-Yu, and 王曼彧. "The roles of integrin betanu and Henji during Drosophila neuromuscular junction development." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/47105064032808850352.
Повний текст джерела國立臺灣大學
分子醫學研究所
99
In response to environmental and physiological stimulations or fluctuations, the synapse has to perform plasticity and also maintains homeostasis. Accumulating evidences support the role of the ubiquitin-proteasome system (UPS) in regulating synapse formation and remodeling, thus maintaining long-term neural circuit plasticity and homeostasis. Here we characterize the function of BTB-Kelch protein, the substrate receptor in the Cullin3 (Cul3)-organized ubiquitin E3 ligase, in the formation and neurotransmission of Drosophila neuromuscular junctions (NMJs). Mutant NMJs lacking henji activity show a dramatic increase in bouton number, including the appearance of numerous satellite boutons. Ultrastructurally, the electron-dense membrane area delineating the presynaptic active zone and the postsynaptic density (PSD) is expanded and the periactive zone is concurrently decreased in henji mutants. The PSD houses glutamate receptors (GluRs) IIA and IIB that show distinct transmissions at Drosophila NMJs. In henji mutants, the GluRIIA abundance is upregulated and the GluRIIB is downregulated. Our electrophysiological results also support a composition shift toward a higher GluRIIA/IIB ratio at henji mutant NMJs. By rescue experiments, we show that Henji acts in the postsynapse to regulate proper NMJ growth and GluRIIA/IIB composition. We further show that Henji controls NMJ growth and GluRIIA/IIB ratio by downregulation of dPak at PSDs. The postsynaptic dPAK marks the PSD area and regulates the GluRIIA abundance. Losing one copy of dpak suppressed the bouton phenotype and GluRIIA abundance in the henji mutant. Also, the intensity and area of dPAK punctates at PSDs were increased in henji mutants. We found that dPAK interacts with Henji, which promotes ubiquitination and degradation of dPak. Therefore, Henji acts at PSDs to restrict both the presynaptic bouton growth and the postsynaptic GluRIIA clustering via controlling dPAK protein level. Several questions remain to be addressed: the subcellular localization of Henji; how dPAK is regulated by Henji during its activation; and how the GluRIIA/IIB balance is controlled by Henji-regulated dPak levels. Some preliminary results and future works will be presented in the thesis. In addition, we also addressed the role of integrin betanu in restricting NMJ growth. In the loss of betanu activity, drastic increase in bouton number was observed. Further, we dissected the downstream signaling of betanu/FAK56 and reported a bifurcating cascade of NF1-regulated cAMP/PKA and Vap-mediated Ras/MAPK pathways.
Arredondo, LaChelle Warbington. "Characterization of the development and function of the neuromuscular junction in Drosophila melanogaster." Thesis, 1998. http://hdl.handle.net/1911/19241.
Повний текст джерелаHuang, Tzu-Han, and 黃子涵. "The Assessment Technique Development of Neuromuscular Control for the Core Muscles in Healthy Athletes." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/90815068374648210794.
Повний текст джерела中山醫學大學
物理治療學系碩士班
104
Background: The connection between core stability and lower extremity injury and lower back pain has been reported.Currently, most assessment methods are used to test muscle endurance and core stability.However,because the activities of athletes tend to exhibit dynamic patterns, muscle strength, muscle power, and neuromuscular control are highly vital components of core stability; therefore, an assessment system that considers multiple components should be established for athletes. Purpose: The aim of this study was to develop acore stability assessment technique for athletes and prove its reliability and applicability in discriminating the core stability conditions among different subjects. Method: This study recruited 20 student athletes who had undergone formal training for more than 5 years.An electromyographic and force platform were used to record data whilethe athletes executed thesecore stability exercise, and their center of pressure (COP) were assessed. Result: Analysis results showed that when the athletes performed the Bird Dog exercise with the right hand and left leg raised, both the COP path length and COP path area demonstrated a positive moderate correlation. Conclusion: Only theBird Dog exercise with the right hand raisedinvolves a correlation between the COP and electromyographic signals, but the difference in core stability among the athletes can be determined because of the significant difference existon core stability movementswas found.
Jacob, Dena A. "The role of cell death in the development of a sexually dimorphic neuromuscular system." 2008. https://scholarworks.umass.edu/dissertations/AAI3315510.
Повний текст джерела"Development of a Novel Low Inertia Exoskeleton Device for Characterizing the Neuromuscular Properties of the Human Shoulder." Doctoral diss., 2020. http://hdl.handle.net/2286/R.I.62916.
Повний текст джерелаDissertation/Thesis
Doctoral Dissertation Mechanical Engineering 2020
Seabrooke, Sara. "Regulatory Effects of the Actin-binding Proteins Moesin and MyosinII on Synaptic Activity at the Drosophila Neuromuscular Junction." Thesis, 2010. http://hdl.handle.net/1807/26383.
Повний текст джерелаAntunes, Inês Curado Batista. "Studying laminins in skeletal muscle development: regulators of muscle stem cells and synaptic organizers." Master's thesis, 2017. http://hdl.handle.net/10451/30947.
Повний текст джерелаO desenvolvimento do músculo, ou miogénese, é um processo bastante conservado entre os vertebrados. Todos os músculos-esqueléticos do tronco e dos membros são provenientes dos sómitos, estruturas epiteliais que se formam em ambos os lados do tubo neural. Os sómitos são posteriormente padronizados em diferentes compartimentos que darão origem a diferentes linhagens celulares. A porção mais ventral do sómito perde a sua estrutura epitelial e forma o esclerótomo, fonte de células precursoras do esqueleto axial. A porção mais dorsal, o dermamiótomo, permanece epitelial e é constituído pelos precursores miogénicos (MPCs) e os percursores da derme, entre outros. Os músculos-esqueléticos iniciam o seu desenvolvimento quando os progenitores no dermamiótomo, que expressam os factores de transcrição Pax3 e/ou Pax7 são induzidos a activar o programa de diferenciação miogénica, controlado pelos factores regulatórios da miogénese (MRF), nomeadamente Myf5, MyoD, Mrf4 e Miogenina. O dermomiótomo encontra-se dividido em três compartimentos distintos: (1) dermomiótomo dorsomediano (2) dermomiótomo central e (3) dermomiótomo ventrolateral. O desenvolvimento dos músculos epaxiais inicia-se no ratinho por volta de E8.5 com a formação do miótomo através da adição das células do dermamiótomo quando estas delaminam do dermomiótomo e povoam a zona ventral ao dermamiótomo para constituir o miótomo. As células precursoras musculares no dermamiótomo, ou células musculares estaminais, que passam a expressar os MRFs, entram no miótomo como mioblastos, mas no miótomo acabam por diferenciar-se em miócitos. O miótomo cresce nos estádios subsequentes com a adição progressiva de células estaminais musculares que diferenciam. Com o início da dissociação do dermamiótomo a E10.5, os progenitores que não se diferenciam acabam por migrar para as massas constituídas por miócitos. Entre E11.5 e E14.5, alguns destes progenitores diferenciam-se em mioblastos primários que fundem com os miócitos para formar as fibras primárias- miogénese primária. Durante os estádios subsequentes até ao nascimento, outra porção de células estaminais que se diferencia em mioblastos, desta vez secundários, que se fundem entre si para formas as fibras secundárias, mas também fundem com as fibras primárias. Esta fase é responsável pelo aumento do tamanho das massas musculares, quer em número de fibras quer no tamanho das mesmas. O sistema de inervação do músculo, mais especificamente a formação das junções neuromusculares (NMJs), sinapses especializadas que se formam entre o músculo e o nervo, desenvolve-se em paralelo com a miogénese. O primeiro contacto entre músculo e nervo antecede o início da miogénese secundária. Por esta altura, já existe uma pré-padronização da distribuição dos receptores de acetilcolina (AChR) no músculo, que será posteriormente remodelada. Dado que a miogénese e a inervação são processos interdependentes para o correcto funcionamento do músculo, estes processos requerem uma comunicação estruturada entre o músculo e o nervo. Durante a miogénese secundária (por volta de E16.5) as células musculares estaminais, positivas para Pax7, migram para o espaço existente entre a fibra muscular e a membrana basal. Esta localização é mantida pelas células estaminais musculares que não se diferenciam durante a miogénese in utero e que constituem a população de células satélite, as células estaminais musculares adultas. Dado que estas se encontram em contacto directo com a membrana basal, a matriz extracelular adquire um papel crucial na regulação do comportamento destas células. Os diferentes elementos que constituem a membrana basal, tais como colagénio, perlecano e laminina permitem que as células estaminais musculares reconheçam o microambiente que as envolve. Além do microambiente que providencia à fibra e às células estaminais musculares durante o desenvolvimento do músculo esquelético, a membrana basal é um componente essencial no desenvolvimento das NMJs. De entre os vários componentes da membrana basal, as lamininas são dos componentes mais bem estudados. As lamininas são trímeros, que apresentam uma estrutura cruciforme ou em T com três cadeias: alpha (α), beta (β) e gamma (γ). Actualmente são conhecidas 16 isoformas diferentes denominadas com base na sua constituição. Por exemplo, a laminina 211 é constituída pelas cadeias α2, β1 e γ1. As lamininas ligam-se principalmente a dois tipos de receptores no músculo: (1) integrinas, receptores transmembranar compostos por duas sub-unidades alpha (α) e beta (β); (2) distroglicano, que se liga intracelularmente à distrofina. Durante a miogénese secundária, as principais isoformas presentes no músculo e nas NMJ são, respectivamente, 211, 411, 511 e 221, 421 e 521. Porém, no músculo adulto, a isoforma que permanece a volta das miofibras é a 211, enquanto nas NMJs adultas continuam presentes as isoformas 221, 421, 521, todas elas cruciais para o desenvolvimento e correcto funcionamento do sistema neuromuscular. As lamininas são determinantes desde cedo no desenvolvimento do músculo-esquelético durante a formação do miótomo através do controlo do balanço entre proliferação e diferenciação das células do dermamiótomo. Em estádios mais tardios do desenvolvimento fetal, as lamininas são parte integrante do microambiente das fibras e das células estaminais musculares que parece ser determinante para o crescimento normal das massas musculares. Em paralelo, as lamininas desempenham papel igualmente preponderante durante o desenvolvimento das junções neuromusculares As células estaminais musculares localizadas entre a membrana basal e a fibra representam no músculo adulto a principal fonte da capacidade regenerativa. Para que a reserva de células estaminais musculares não se esgote é necessário garantir que exista um equilíbrio entre a proporção de células que se mantêm quiescentes, as células que são activadas e as células que se diferenciam no momento da regeneração. A membrana basal que hospeda estas células representa um elemento determinante em distintas vias de sinalização que operam no sentido de instruir as células a manterem-se quiescentes, a activar, a proliferar ou diferenciar. A sinalização Notch destaca-se como reguladora deste processo. Quando abolida, as células estaminais musculares diferenciam-se precocemente sem a necessária proliferação que permite manter a população e desta forma a população acaba por esgotar-se. A Distrofia muscular congénita merosina negativa (MDC1A) é um tipo de distrofia causado por mutações no gene LAMA2 que levam à perda das lamininas 211 e 221 da membrana basal das fibras e junções neuromusculares, respectivamente. Esta doença é caracterizada por fraqueza muscular, neuropatia, dificuldades respiratórias, entre outros sintomas. Neste estudo, usámos o modelo de ratinho dyW como modelo de estudo para a MDC1A. Estudos recentes do nosso laboratório demonstraram que no ratinho, o desenvolvimento da MDC1A inicia-se in utero entre E17.5 e E18.5. O início desta distrofia é demarcado por uma diminuição significativa no número de células positivas para Pax7, em paralelo com uma diminuição do crescimento do músculo fetal. O trabalho realizado nesta tese teve como objectivo compreender melhor como é que as células musculares constroiém o seu microambiente e de que forma alterações no microambiente tanto das células musculares como das junções neuromusculares influencia o crescimento do músculo fetal. Numa primeira abordagem, avaliámos a capacidade das células musculares, tanto as células estaminais musculares como as fibras, de produzirem e montarem as matrizes de laminina. Os nossos resultados demonstram que numa fase inicial da miogénese secundária, as células estaminais musculares são as principais produtoras de laminina no músculo e montam as suas matrizes de laminina mesmo na ausência das fibras. Durante fases mais tardias da miogénese secundária, as fibras passam a expressar os diferentes genes de laminina e a sua presença parece ser importante para que as matrizes de laminina sejam mantidas no microambiente das células estaminais musculares. Desta forma, este trabalho revela que as células musculares desempenham papéis diferentes na construção das matrizes de laminina em fases distintas da miogénese secundária e que as células estaminais e as fibras são interdependentes na construção das matrizes de laminina. Numa segunda abordagem, esta tese teve como objectivo compreender em maior detalhe o papel da laminina 221 durante a formação das NMJs e compreeender a sua influência no início/progressão da MDC1A. Para tal, estudámos o desenvolvimento das NMJs durante a miogénese secundária em ratinhos dyW. Os nossos resultados revelam que enquanto as lamininas α2 e α4 não aparentam ter um contacto directo com sinapse a E15.5, as lamininas α5 apresentam uma proximidade com a sinapse. Esta dinâmica não parece estar alterada na ausência da laminina α2 (211/221). Contudo, a nossa análise do desenvolvimento das NMJ na ausência de laminina 221, ainda que preliminar, sugere que a distribuição dos receptores de acetilcolina está alterada e que há uma tendência para que os receptores se encontrem mais dispersos ao longo do músculo na ausência de lamininas α2. Estes resultados apontam para um papel das lamininas na agregação dos receptores junto da fenda sináptica. Em suma, o trabalho desenvolvido ao longo desta tese realça a complexidade das dinâmicas de produção e construção das matrizes de laminina durante a miogénese secundária. Os dados desta tese exemplificam igualmente a diversidade de microambientes aos quais as células estaminais estão sujeitas durante diferentes fases da miogénse secundária. Esta tese analisa em particular o papel das lamininas α2 durante o desenvolvimento das NMJs e fornece novas evidências acerca da influência da inervação do músculo no início da MDC1A.
MDC1A is a crippling neuromuscular disease caused by the absence of the α2-chain of laminins 211/221, major components of basement membranes. The onset of this disease during development in utero is marked by impaired muscle growth which correlates with a reduction in the number of mononucleated muscle cells in the fetal muscle masses (Nunes et al., 2017). Skeletal muscle development starts during early embryogenesis, when the dermomyotomal Pax3- and/or Pax7-positive muscle precursors cells are induced to enter the myogenic program and subsequently delaminate from the dermomyotome to form the myotome. Later on, when the dermomyotome dissociates, Pax3- and/or Pax7-positive muscle stem cells are released, some of which differentiate into myoblasts and fuse with myotomal cells or with each other, forming the primary myofibers during primary myogenesis that occurs between E11.5 and E14.5. The primary myofibers later serve as a scaffold for the formation of secondary myofibers and secondary myoblasts fuse with both primary and secondary myofibers to increase their size. Motor axons enter the muscle masses in parallel with primary myogenesis, but it is during secondary myogenesis (between E14.5 until birth) that the nerve contacts the muscle, and proper innervation is essential for normal fetal muscle development. During mid-secondary myogenesis, the Pax7-positive muscle stem cells become closely associated with the myofibers and their basement membrane. Laminin 211 and 221 are assembled around the adult myofiber and synaptic endplate, respectively, and are known to play important roles both in myofiber and neuromuscular junction development. In this thesis we aimed to contribute to the study of the fetal myogenesis defect in dyW mice in two ways: First, we asked what cell types produce laminins during fetal myogenesis. We performed a detailed analysis of laminin production and assembly in fetal muscles at stages preceding the onset of MDC1A. We found that mononucleated cells, including Pax7-positive cells, are a major source of laminins at the beginning of secondary myogenesis, but during later stages of secondary myogenesis, myofibers also express laminin genes. This suggests that Pax7-positive muscle stem cells play a major role in constructing the laminin microenvironment in the fetal muscles. We then used the Myf5cre-NICD mouse model (Mourikis et al., 2012) where Pax7-positive cells are unable to differentiate and thus do not form muscle fibers. We found that Pax7-positive cells at E14.5 produce and assemble laminins 211, 411 and 511, but at E17.5, the capacity to produce laminins is greatly diminished as they only produce laminin 511. These results indicate that Pax7-positive cells at E17.5 require the presence of myofibers to produce and assemble laminins 211 and 411. Second, since it is known that fetal myogenesis depends on innervation, we used the dyW mouse model, which has a mutation in the Lama2 gene, to assess the role of laminin 211/221 during neuromuscular junction development. We found that laminin 521 is closely assembled around the synapse, while laminins 421 is present, but does not seem to be in direct contact with the synapse. In the wildtype, laminin 221 has a distribution like laminin 421. However, our spatial analysis showed that α2-laminin deficient synapses tend to have a less clustered organization compared to wildtype ones and display a deficient AChR patterning. Based on these results, we hypothesize that laminin 221 might play a crucial role in NMJ development and that this may contribute to the onset of the fetal myogenesis defect in dyW mice. Together, our results provide new insights into laminin production and assembly during fetal muscle development and provide new indications into the mechanism underlying disease onset during development in utero in a mouse model for MDC1A.