Dissertations / Theses on the topic 'NNos'
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Simmers, Jessica L. "nNos localization, muscle function and atrophy in skeletal muscle disorders." Thesis, The Johns Hopkins University, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=3573097.
Full textIn skeletal muscle, loss of neuronal nitric oxide synthase (nNOS) from the sarcolemma has been observed in a few muscular dystrophies and myopathies. However, the extent of this phenomenon, its mechanism, and its physiological impact are not well understood. Using immunofluorescent staining for nNOS, a survey of 161 patient biopsies found absent or reduced sarcolemmal nNOS in 43% of patients. Patient mobility and muscle functional status correlated with nNOS mislocalization from the sarcolemma. Mouse models of inherited and acquired myopathies showed similar loss of sarcolemmal nNOS and impaired mobility and muscle function. A proteomic approach, using mass spectrometry and differentially labeled control and steroid-induced myopathy (SIM) mouse samples, found novel nNOS binding proteins including alpha-actinin-3 (ACTN3), which exhibited decreased interaction with nNOS after steroid treatment. It revealed a potential explanation for impaired muscle function in SIM as nNOS interactions were lost at the sarcomere and gained at the sarcoplasmic reticulum impairing contractility. Treating nNOS-deficient mice with steroids demonstrated that loss of sarcolemmal nNOS reduces muscle contractility and strength in SIM through increased nitric oxide (NO) signaling. In SIM mice treated with a nitric oxide donor and steroids, nitric oxide partially protects the muscle from atrophy and improves muscle fatigability and recovery suggesting nNOS mislocalization also decreases NO availability. These findings show that loss of sarcolemmal nNOS is a common phenomenon that negatively impacts muscle function. Therapeutic strategies targeting nNOS or NO signaling need to allow for the complexity of local nitric oxide content and cellular context.
BALDELLI, SARA. "Ruolo dell'ossido nitrico sintasi neuronale (nNOS) nella modulazione dell'omeostasi redox intracellulare." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2009. http://hdl.handle.net/2108/861.
Full textNitric oxide (NO) plays an important role in both physiological and pathophysiological mechanisms involving properties at the chemical, cellular, and physiological levels. The relatively low concentration of NO required being an antioxidant suggests that in addition to its involvement with cyclic GMP, this radical molecule serves to counterbalance oxidative stress. This balance between NO and oxidative stress provides an important regulatory mechanism in numerous physiological effects. Imbalance in this redox symbiotic relationship can lead to different pathophysiological conditions. Here we demonstrate the neuroprotective role played by nNOS/NO in counteracting the ROS-mediate ciotoxicity, induced by treatment with garlic derivatives. In particular, we found that, besides their role in promoting growth arrest and apoptosis, either oil-soluble derivatives DADS or water GE significantly increased the content of nNOS in neuronal cell lines. Next to the antioxidant action of NO, each cell is equipped with an extensive antioxidant system to counteract their harmful properties directly by interception or indirectly through reversal of oxidative damage. In central nervous system, the antioxidant defence system and nNOS may interact to ensure the integrity and homeostasis of neuronal cells. Especially in the nervous system the nNOS/NO may directly or indirectly modulate the activity and expression of antioxidant defence systems. Indeed, we further analysed the influence of endogenous overproduction on NO on the intracellular antioxidants SOD1 and GSH in cell lines of neuronal and non-neuronal origin. We report that nNOS over-expression induced a NO-dependent increase in the concentration of GSH thus reinforcing the idea that it represents a protective agent against NO cytotoxicity. On the other hand, the nNOS over-expression causes a NO-indipendent down-regulation of SOD1 in terms of mRNA, protein and activity levels.
SAGRATI, ANDREA. "Neuronal nitric oxide synthase positive cells in the human corpus callosum and indusium griseum." Doctoral thesis, Università Politecnica delle Marche, 2021. http://hdl.handle.net/11566/291083.
Full textThe aim of the present study is to investigate the possible mechanism for the control of cerebral blood flow in the corpus callosum (CC), that could explain the BOLD effect previously found (Fabri et al., 2011). The presence, number, distribution and morphology of neuronal Nitric Oxyde Sinthase (nNOS) positive cells was investigated in the corpus callosum (CC) and indusium griseum (IG). Nitric Oxyde (NO) is a gaseous neurotransmitter largely diffused in the brain, whichexerts a powerful vasodilatory effect, and therefore it can contribute to regulate the cerebral blood flow. Sagittal serial sections from paraffin or frozen autoptic specimens of human adult CC and overlying IG were processed for immunohistochemistry and immunofluorescence analysis, using an antibody against the neuronal form of the enzyme Nitric Oxyde Synthase (nNOS). The stainings revealed the presence of many nNOS immunopositive cells. By double labeling technique with immunofluorescence at confocal microscopy, it has been shown that in the CC both neurons and astrocytes positive to nNOS antibody were present, and their number varied in different conditions, as detailed below. In the IG, only neurons nNOS positive were found. Neurons showed different morphologies, were more numerous 1 mm apart from the medial line in IG and 4 mm in CC, with a peak over the body of the CC. In some cases, they were located at the boundary between IG and CC, more densely packed in proximity to the pial arteries penetrating into the CC. The significant presence of nNOS immunopositive neurons in these two structures suggests that they might have a role in the neurovascular regulation of CC, moreover the IG could plays a functional role in the adult brain. The presence of nNOS positive astrocytes in the human CC has been here demostrated for the first time. As previously mentioned, their number and distribution varied in different conditions: nNOS positive astrocytes were absent in samples from subjects deceased after a short hypoxia; their number and labeling intensity increased with the hypoxia prolongation. Neuronal NOS immunopositivity of CC astrocytes seems thus related to the hypoxia duration and the consequent brain damage.
Cheung, Nathan Yiutung. "Serotonin receptor and neuronal nitric oxide synthase expression in the rat brain : implications for MDMA toxicity." Thesis, King's College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368095.
Full textJähne, Sebastian [Verfasser]. "Kompensationsmechanismen im Skelettmuskel von neuronaler Stickstoffmonoxid-Synthase (nNOS) defizienten Mäusen / Sebastian Jähne." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2010. http://d-nb.info/1027814905/34.
Full textLim, Gregory B. S. "nNOS-derived nitric oxide modulation of the ryanodine receptor calcium release channel." Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.533867.
Full textMcNamara, Tanner. "ENOS and nNOS contribution to reflex cutaneous vasodilation during dynamic exercise in humans." Thesis, Kansas State University, 2012. http://hdl.handle.net/2097/13788.
Full textDepartment of Kinesiology
B.J. Wong
Recent data suggests nNOS mediates the NO-component of reflex cutaneous vasodilation with passive heat stress. Our hypothesis was nNOS, but not eNOS, inhibition would attenuate reflex cutaneous vasodilation during dynamic exercise. Protocol 1: subjects performed a VO[subscript]2 peak test on a supine cycle ergometer. Protocol 2: with experimental arm at heart level subjects cycled in supine posture at 60% VO[subscript]2 peak to raise core temperature (Tc) 0.8-1.0°C (35-45 min). In protocol 2 subjects were equipped with 4 microdialysis fibers on the forearm and each randomly assigned as: 1) lactated Ringer’s (control); 2) 5mM NPLA (nNOS inhibition); 3) 10mM L-NIO (eNOS inhibition); and 4) 20mM L-NAME (non- selective NOS inhibition). At the end of protocol 2 all sites were locally heated to 43°C and infused with SNP to elicit maximal dilation. Mean arterial pressure (MAP), skin blood flow via laser- Doppler flowmetry (LDF), and Tc via ingestible telemetric pill were measured; cutaneous vascular conductance (CVC) was calculated as LDF/MAP and normalized to maximum. In protocol 2 there was no significant difference between control (62±5 %CVCmax) and NPLA (61±6 %CVCmax). L-NIO (38±4 %CVCmax) and L-NAME (41±7 %CVCmax) significantly attenuated CVC compared to control and NPLA (p<0.001 all conditions). There was no difference between L-NIO and L- NAME. We conclude eNOS, not nNOS, contributes to reflex cutaneous vasodilation during dynamic exercise.
Sangüesa, Ferrer Juan F. "Modulation fonctionnelle et distribution du canal calcique Cav3. 2 : rôle de la nNOS." Montpellier 1, 2008. http://www.theses.fr/2008MON1T015.
Full textSato, Vinicius Antonio Hiroaki. "Participação da serotonina no efeito tipo-antidepressivo induzido pela inibição da nNOS no hipocampo de ratos." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/17/17133/tde-22062011-090727/.
Full textIntroduction: Nitric oxide (NO) has been suggested to play an important role in the neurobiology of stress adaptation and depression. In fact, systemic or hippocampal administration of neuronal NO synthase (nNOS) inhibitors induces antidepressant-like effects in animal models. Recent evidence indicates that the systemic effects of nNOS inhibitors are dependent on serotonin levels in the brain. The serotonergic system of the dorsal hippocampus (DH), through the activation of serotonin 1A (5-HT1A) receptors, is proposed to mediate stress adaptation and the behavioral effects of antidepressant drugs. Therefore, the aim of the present study was to test the hypothesis that the antidepressant-like effects induced by nNOS inhibition into the hippocampus would be mediated by a facilitation of the local serotonergic neurotransmission and subsequent 5-HT1A receptor activation. Methods: Male Wistar rats with guide-cannulae aimed at the DH were submitted to the pretest session (PT - 15 minutes of swimming) and received local administrations of the drugs: n-propyl-L-arginine (NPA, selective nNOS inhibitor: 0.00001 - 1 nmol/0.5 µL), fluoxetine (SSRI: 1, 3 and 10 nmol/0.5 µL), WAY100635 (selective 5-HT1A antagonist: 1, 3 and 10 nmol/0.5 µL) or vehicle (0.5 µL). One day later, the immobility time was registered at a 5 minutes swimming test session. All protocols were approved by a local ethical committee (Proc. N. 08.1.1133.53.4.) Results: The intrahippocampal administration of NPA or fluoxetine reduced the immobility time in animals submitted to the forced swimming test, an antidepressant-like effect in this model. WAY100635 did not induce any effect per se, but it was able to block the effects induced by fluoxetine or NPA. Conclusions: Inhibition of nNOS, by NPA, or inhibition of serotonin reuptake, by fluoxetine, in the DH induced antidepressant-like effects of similar magnitude. The fact that pretreatment with WAY100635 was able to block NPA- and fluoxetine-induced effects indicates that both effects are mediated by a facilitation of the local serotonergic neurotransmission and subsequent activation of 5-HT1A receptors. Therefore, these results suggest that increased NO levels in the DH could impair local serotonergic neurotransmission and, thus, predisposes to the development of stress-induced behavioral consequences, such as depressive-like behaviors.
Sato, Vinicius Antonio Hiroaki. "Substratos neurais envolvidos com o desenvolvimento do comportamento de desamparo em ratos: possível envolvimento do NO." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/17/17133/tde-20072016-091556/.
Full textRecently, nitric oxide (NO) has been related with the neurobiology of depression. The NO synthase (NOS) inhibition induces antidepressant-like effects in animal models and there is an increase in the NOS expression in limbic structures of depressed patients or in stress exposed animals. Besides, it is well known that stressful events causes an increase in limbic structures neuronal activation and that antidepressant treatment as well as NOS inhibition attenuates this effect. However, it is still unknown how the limbic nitrergic system is related with depression-related behaviors. Then, the aim of this work is to test the hypothesis that the helplessness behavior development (a depression-related behavior) in rats would be induced by an increased activity of nNOS-containing neurons in structures related with the neurobiology of stress responses. Furthermore, the antidepressant-like effect induced by antidepressants treatment in this model would share a final effect, decreasing the activation of such neurons, and decreasing the levels of NO in these structures. For this aim, male rats were submitted to the learned helplessness model and treated with antidepressants. After the test, immunohistochemistry assay were performed, with double labeling for c-Fos (Fos-IR; neuronal activity marker) and nNOS (nNOS-IR). The repeated treatment with desipramine (DES, 25 mg/kg but not 12,5mg/kg), fluoxetine (FXT, 15 mg/Kg, but not 30 mg/Kg) and imipramina (IMI, 15 mg/KG) induced antidepressant-like effects in the learned helplessness test (LH). The acute treatment with IMI, but not with DES or FXT, induced the same effect. The repeated treatment with DES, FXT or IMI also increased the number of intertrial crossings in the LH, but not the locomotor activity score on the open field score. The repeated treatment with DES decreased the number of Fos-IR into the basolateral amygdala (BlAm), lateral amygdala (Lam), medial prefrontal cortex (mPFC), CA1 and CA3 regions of the dorsal hippocampus (dHPC), and CA3 region of the ventral hippocampus (vHPC). The acute treatment with DES increased the Fos-IR into the central amygdale (CeAm), medial amygdala (MeAm), and CA1 and CA3 regions of the dHPC. The repeated treatment with FXT decreases the number of Fos-IR into the BlAm and Lam, while the acute treatment increases the Fos-IR into the CeAm. The repeated treatment with IMI increased the nNOS-IR into the MeAm and the double- labeled cells into the bed nucleus of stria terminalis (BST); and decreased the Fos-IR into the CA1 region of the dHPC and into the parvocellular region of the paraventricular nucleus of the hypothalamus. Finally, positive correlations between the number of Fos-IR and the number of failures in escaping or avoiding the foot shocks on the LH were found into the BlAm, Lam, CA1 and CA3 of the dHPC, and CA3 of the vHPC, i.e., with more activated cells into these structures mentioned, more foot shocks the rats received. These results are (partially) corroborated with previous scientific papers, showing the analyzed structures participation in the learned helplessness behavior as well as in the antidepressant effect of antidepressant administration. Within this context, the BST would work as a relay center, processing the information coming from the mPFC, HPC and amygdaloid nuclei, and sending the output to the PVN, modulating the HPA axis. This work open some questions about the identification of specific nNOS-containing neuronal subpopulations, aiming to clarify their role in the stress response, and searching for the formulation of a more complete scenario of the nitrergic system participation in this complex emotion-regulating neurocircuit
Santos, Jaqueline Rocha Borges dos. "Participação da enzima nNOS na sensibilização cruzada entre estresse e etanol em camundongos Swiss." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/42/42136/tde-15032014-084536/.
Full textThe objective of this work was to investigate behavioral alterations produced by ethanol (ET) and chronic unpredictable stress (CUS) in adolescent (ADL) and adult (AD) mice, studying the nNOS enzyme activity. In AD mice was also studied the nNOS activity through the NMDA receptor in the cross-sensitization between immobilization stress (IS) and ET, by using dizocilpine (DZP) as a pretreatment. The results demonstrate cross-sensitization between CUS and ET in the ADL and AD mice. There was an increase in the nNOS activity in hippocampus (HP) and frontal cortex (FC) of AD submitted to CUS. This effect was attenuated by ET. The cross-sensitization in ADL increased the nNOS activity in FC. The 7-nitroindazole pretreatment inhibit cross-sensitization between CUS and ET in ADL and AD, signaling the nNOS participation. DZP potentiates cross-sensitization between IS and ET and decreased the nNOS activity in HP and FC of animals submitted to IS. CUS and IS induce behavioral sensitization to the ET and nNOS participate in the cross-sensitization between CUS/IS and ET.
Lu, Chieh-Ju. "Neuronal nitric oxide synthase-CAPON regulation of cardiac sympathetic activity in the development of hypertension." Thesis, University of Oxford, 2015. http://ora.ox.ac.uk/objects/uuid:1204dec9-9f09-458d-b361-c8d14589fcd1.
Full textEisenhauer, Astrid. "Die kognitiven Defizite in einem Sepsismodell bei Ratten sind auf eine Herunterregulierung der nNOS zurückzuführen." [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=970030274.
Full textMolza, Anne-Elisabeth. "Etude in silico du complexe impliquant le domaine central de la Dystrophine, le domaine PDZ de la nNOS, l'Actine filamenteuse et les Phospholipides membranaires." Thesis, Rennes 1, 2015. http://www.theses.fr/2015REN1B018.
Full textDystrophin is a large protein encoded by DMD gene and located under the plasma membrane of muscle fibers. It plays an essential role in maintaining the integrity of muscle cells during contraction/relaxation cycles. This filamentous protein is composed of four structural domains including the central domain consisting of 24 spectrin-like repeats and four hinges. Each repetition is folded in three α-helices in a ‘coiled-coil’ assembly. Mutations in the DMD gene leads to Duchenne muscular dystrophy (DMD) and Becker (MDBs), which are accompanied by frequent plasma membrane ruptures, due to the loss or modification of dystrophin protein. There are very few structural data available concerning the central domain of dystrophin, which is subject to many mutations involved in DMD and BMD diseases. However, the description and the understanding to an atomic level of dystrophin structure and its interaction is essential for optimization of therapies. Given the impossibility to solve its structure by X-ray crystallography or NMR, structural data of the dystrophin central domain were acquired by small angles X-rays scattering (SAXS, Small Angles X-ray Scattering). This thesis presents the development of an innovative multi-scale approach combining experimental SAXS and in silico derived data, allowing the reconstruction of high-resolution models of dystrophin central domain fragments. Structural data were also obtained on a mutated dystrophin frequently observed in BMDs. Furthermore, we also mapped the interactions of the central domain with two of its majors functional partners, Filamentous actin and neuronal nitroxyde synthase (nNOS) and proposed models of the related macromolecular complexes. At long-term, all of these results will allow optimization of therapies for the treatment of muscular dystrophies
Given, Alexis. "Models of Epsilon-Sarcoglycan Gene Inactivation and their Implications for the Pathology of Myoclonus Dystonia." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/23790.
Full textHeaton, Daniel Anthony. "Role of nNOS in the autonomic control of cardiac excitability in cardiac physiological and pathophysiological states." Thesis, University of Oxford, 2005. http://ora.ox.ac.uk/objects/uuid:5dfc213d-7846-485d-93f1-1635a0018ef0.
Full textCoelho, Camila Henriques. "Análise da inibição da óxido nítrico sintase neuronal (nNOS) na liberação de vasopressina durante sepse experimental." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/60/60135/tde-30102009-022744/.
Full textThe pathophysiology of sepsis is caracterized by hypotension accompanied by increase of vasopressin secretion (AVP) in early phase and decrease during late phase. This hypotension is due, in part, to the increase of nitric oxide (NO) production, that, like other mediators, shows high production during sepsis. Nitric oxide synthase (NOS) is responsible by synthesis of NO. The neuronal isoform of NOS is present in skeletic muscle, testicles, prostate, skin and vasopressinergics neurons of hypothalamus. The present work evaluated the participation of nitric oxide produced by neuronal NOS in temporal vasopressin secretion during experimental sepsis. Rats Wistar received intraperitoneal injection of 7-nitroindazole (50 or 80 mg/kg), an inhibitor of neuronal nitric oxide synthase activity, or DMSO 10% + sesame oil in the proportion 1:9 (vehicle) and after 30 minutes, they were submited to septic stimulus by cecal ligation and puncture (CLP) or to sham operation. In one of the groups, the survival rate was evaluated during 5 days. In other group, the animals were decapited 0, 4, 6, 18 and 24 hours after CLP and the blood was processed to determinate haematocrit, serum sodium, osmolality, proteins, glucose, creatinine, serum nitrate, and plasma AVP. Neurohypophysis was removed to determination of vasopressin content, and hypotalamus was dissected to determinate total NOS activity. Mortality observed after CLP was not affected by periferal injection of 7-nitroindazole (50 mg/kg) as well as haematocrit, glucose and nitrate increase. Serum sodium and plasma protein decreased after CLP and the treatment antecipated the loss protein, and delayed serum sodium decrease. CLP animals didn\'t show creatinine and osmolality alterations, but when treated with 7-nitroindazole, showed increase 6 and 18 hours, and decrease 4 hours, respectively. NOS activity in hypothalamus increased 4 and 24 hours after CLP, and was reduced with 7-NI pretreatment (50 and 80 mg/kg respectively). AVP neurohypophysis content diminished 4, 6 and 18 hours after CLP and 7-NI reduced the content just at 0 and 6 hours. Vasopressin plasma concentration increased just 6 hours after CLP and 7-NI pretreatment didn\'t alter this parameter. We concluded that NO produced by neuronal NOS doesn\'t have a substantial role in vasopressin secretion during experimental sepsis.
Lewis, Sophronia. "The effect of ablation and acute inhibition of plasma membrane calcium ATPase 4 (PMCA4) with a novel inhibitor on isolated mouse mesenteric resistance arterial contractility." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/the-effect-of-ablation-and-acute-inhibition-of-plasma-membrane-calcium-atpase-4-pmca4-with-a-novel-inhibitor-on-isolated-mouse-mesenteric-resistance-arterial-contractility(676a26ea-867e-4947-9544-76b356fce23a).html.
Full textIyomasa, Daniela Mizusaki. "Avaliação dos efeitos do estresse crônico sob a ansiedade e a sensibilidade nociceptiva em ratos mantidos em ambiente enriquecido." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/59/59134/tde-24052018-222146/.
Full textAdaptive responses to stress may be accompanied by changes in emotional behaviors, in particular related to fear and anxiety, as well as changes in pain sensitivity. Furthermore, the role of nitric oxide in brain areas related to defensive behavior has been investigated. Although several evidences have shown that environmental enrichment improves memory processes, learning and nociceptive responses, the relationship between chronic stress and the advantages of using environmental enrichment is still poorly investigated. The present study aimed to investigate whether environmental enrichment promotes alteration of the emotional behavior, nociceptive sensitivity, as well as immunoreactivity to neuronal nitric oxide synthase (nNOS) in the central nucleus of the amygdala, hippocampal formation and dorsolateral periaqueductal gray matter in rats submitted to social isolation stress or chronic unpredictable stress and reared in enriched environment or standard environment. Male Wistar rats (~ 70g) were randomly divided into two major experimental groups: Standard Environment (Standard) or Enriched Environment (EE), maintained for 38 days. Each group was subdivided according to the type of chronic stress: Control (without stress), Social Isolation (for 38 days) and Chronic Unpredictable Stress (from day 28 to day 37). At the end of the experimental time (day 38), the rats were evaluated for emotional behavior by elevated plus maze (EPM) and light/dark box (LDBT) tests and nociceptive sensitivity by the hot plate test (which was performed in two steps , the first being measured on day 0 and the other on day 38). Euthanasia of rats occurred on day 39, to collect the brain for nNOS immunoreactivity analysis. Taking into account emotional behavior and nociceptive sensitivity, the different types of chronic stress decreased the percentage of time, the frequency of entry of the open arms, end-arm exploration and the head dipping frequency in the EPM, despite of not altering the nociceptive sensitivity. On the other hand, environmental enrichment increased the percentage of time, the frequency of entry of the open arms and the end arm-exploration in the EPM test, although it did not alter the nociceptive sensitivity. Increased immunoreactivity to nNOS in hippocampal formation was observed in different types of chronic stress. In particular, in the CA3 region there was a significant interaction between stress factors due to social isolation and maintenance environment. Thus, the results obtained in this study suggest that hippocampal formation plays an important role in the anxiogenic effect exerted by the different types of chronic stressors (represented here by social isolation and by chronic chronic stress) probably due to the activation of the nitrergic system and it is suggested that environmental enrichment can prevent of anxiety-like behavior.
Bird, Diane Carol. "An investigation into the role of neuronal nitric oxide synthase (nNOS) in the phencyclidine mouse model of schizophrenia." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0015/MQ57249.pdf.
Full textHirsch, Tamara. "A behavioural evaluation of the potential of nNOS inhibitors to control dyskinesia in animal models of Parkinson's disease." Thesis, King's College London (University of London), 2012. https://kclpure.kcl.ac.uk/portal/en/theses/a-behavioural-evaluation-of-the-potential-of-nnos-inhibitors-to-control-dyskinesia-in-animal-models-of-parkinsons-disease(777432ce-93ec-429c-a5c8-41d42dd2069b).html.
Full textDenadai, Magda Aline. "Efeitos do 7-nitroindazole, um inibidor da sintase neuronal do oxido nitrico (nNOS), sobre o condiciomaneto contextural em pombos." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314745.
Full textDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-08-11T20:16:54Z (GMT). No. of bitstreams: 1 Denadai_MagdaAline_M.pdf: 823511 bytes, checksum: 1887972f9e5047fecbd7195247b586a8 (MD5) Previous issue date: 2008
Resumo: O óxido nítrico (NO), um neurotransmissor não convencional, tem papel importante em processos neurobiológicos de comportamento e de memória. Sua síntese é mediada por três isoformas de sintase do óxido nítrico (NOS): a neuronal (nNOS), a endotelial (eNOS) e induzível (iNOS). Este trabalho analisou o efeito do 7-nitroindazole (7-NI), um inibidor seletivo da nNOS, no condicionamento clássico aversivo em pombos. Foram usados 4 grupos: tratados com 7-NI (grupo 7-nitroindazole; G7-NI, n=5), tratados com óleo de amendoim (grupo veículo; GV, n=5), controle/sem tratamento (grupo controle; GC, n=5) e grupo não tratado/não condicionado (grupo manipulação; GM, n=5). A administração i.p. de 7-NI (25 mg/kg), ou do óleo de amendoim foi feita imediatamente após o treinamento. O G7-NI, o GV e o GC receberam três associações som-choque (5°, 10° e 15º minutos) numa sessão de 20 min. O teste a o contexto foi realizado 24 horas depois. As sessões foram gravadas para posterior transcrição e análise comportamental. A ocorrência da resposta de congelamento durante o treino não diferiu entre os grupos (p>0,05), mas durante o teste foi menor para o G7-NI em comparação ao treino (p<0.01) e aos demais grupos no teste (p<0.001). A atividade da NOS dependente de Ca++ no hipocampo foi menor no G7-NI do que nos outros grupos (p<0,01). Análise por Western blot indicou aumento na expressão de nNOS no G7-NI (p<0,05). A administração sistêmica de 7-NI teve um efeito amnésico sobre a memória contextual aversiva, indicando que a atividade da NOS dependente de Ca++ é importante para os processos de condicionamento clássico aversivo em pombos.
Abstract: Nitric oxide (NO) is an unsual neurotransmitter that plays an important role in neurobiological functions underlying behavior and memory. NO synthesis and release can be mediated by three isoforms of NO synthases (NOS): neuronal (nNOS), endothelial (eNOS) and inducible (iNOS). This study examined the effect of 7-nitroindazole (7-NI), a selective nNOS inhibitor, on contextual fear conditioning in pigeons. Four groups of pigeons were used: treated with 7-NI (7-NI; n=5), treated with peanut oil (Vehicle; n=5), non treated controls (Control; n=5) and non treated and no-trained controls (Non-trained; n=5). Treatment consisted in 7-NI (25 mg/kg; i.p.) or vehicle (peanut oil) administration, immediately after training. All the animals were trained in one 20 min session during which three tone-shock pairings (5th, 10th and 15th minutes) were presented. The test to the context was conducted 24h later. Behavioral categories were analyzed through the transcription of video-tapes of the sessions. The groups 7-NI, Vehicle and Control showed no significant differences in freezing during the conditioning session (p>0.05). During the test to the context the group 7-NI expressed significantly lower freezing as compared to Vehicle and Control (p<0.05). The 7-NI pigeons showed lower hippocampal activity of Ca++ dependent-NOS than Vehicle and Control groups (p<0.01). Western blot analysis indicated significant increase in nNOS expression (p<0.05). The systemic administration of 7-NI induced amnestic effects on contextual fear memory that evidence that Ca++-dependent NOS activity is required for fear conditioning in pigeons.
Mestrado
Fisiologia
Mestre em Biologia Funcional e Molecular
Eskandari, Julia Mirjam [Verfasser], Viktoria [Akademischer Betreuer] Kolb-Bachofen, Daniela [Akademischer Betreuer] Bruch-Gerharz, and Ulrich [Akademischer Betreuer] Germing. "Untersuchungen zur nNOS an psoriatischer Haut / Julia Mirjam Eskandari. Gutachter: Daniela Bruch-Gerharz ; Ulrich Germing. Betreuer: Viktoria Kolb-Bachofen." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2011. http://d-nb.info/1018272518/34.
Full textSchonhoff, Christopher M. "The Regulation of nNOS During Neuronal Differentiation and the Effect of Nitric Oxide on Hdm2-p53 Binding: a Dissertation." eScholarship@UMMS, 2000. https://escholarship.umassmed.edu/gsbs_diss/57.
Full textKececioglu, Ekin. "Analysis Of Immunoreactivity Of Nos Isoforms (nnos, Enos, Inos) In Hippocampus Of Young Rats Classified As Good And Poor Learners." Master's thesis, METU, 2012. http://etd.lib.metu.edu.tr/upload/12614994/index.pdf.
Full textgood&rdquo
and &ldquo
poor&rdquo
learners. The NOS isoforms were visualized on coronal hippocampal sections using fluorescent immunohistochemistry technique and n- and eNOS images were processed using ImageJ software, while iNOS immunoreactivity (IR) was assessed by counting immunoreactive cells. In this study, overall hippocampal levels of nNOS were significantly higher than those of eNOS and iNOS. The level of n and eNOS was higher in CA1 compared to DG/hilus areas, but lower than that in CA3 region. The expression of iNOS was the highest in CA1 and the lowest in hilus region. nNOS IR was significantly higher in &ldquo
poor&rdquo
than in &ldquo
good&rdquo
learners but only in CA1 region. No significant between-group differences were found in eNOS expression. iNOS expression was higher in &ldquo
poor&rdquo
learners but it did not reach the required significance level.
Barua, Anupama. "The role of neuronal nitric oxide synthase (nNOS) in ischaemia/reoxygenation-induced injury and in protection of the mammalian myocardium." Thesis, University of Leicester, 2010. http://hdl.handle.net/2381/8754.
Full textPereira, Linus de Queiroz. "Silenciamento da expressão da enzima óxido nítrico sintase neuronal (nNOS) em linhagem de neuroblastoma via siRNAs sintéticos em dupla fita." reponame:Repositório Institucional da UnB, 2011. http://repositorio.unb.br/handle/10482/20854.
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O óxido nítrico (NO) é formado pelas enzimas NO sintases e desempenha papel na patogênese da neurodegeneração. NO sintase neuronais são expressas em áreas cerebrais lesionadas e sua inibição reduz efeitos de agentes neurotóxicos. O atual estudo desenvolveu siRNAs (small interfering RNAs) direcionados a duas sequências do RNAm de nNOS, presentes nos exons 2 e 28. Primeiramente, foi utilizado o algoritmo Biopredsi para identificar alvos de RNAi. Foi realizada síntese química dos siRNA duplos com 21 nucleotídeos - exon2_hnNOS e exon28hnNOS (Qiagen). Células de neuroblastomas SH-SY5Y receberam 150 pmol ou 300 pmol de cada siRNA estruturado em lipossomas (Lipofectamine 2000®, Invitrogen). Utilizou-se o controle negativo scramble All-Stars® (Qiagen). Os meios de cultivo celular utilizados foram Optimen® e DMEM® (Gibco), pelas primeiras 6h e para as 24h de incubação restantes, respectivamente. O conteúdo de RNAm de nNOS foi quantificado por PCR em tempo real via SYBR Green®; os efeitos de silenciamento foram apresentados pela expressão relativa (2-ΔΔCT). O nível de RNAm foi reduzido para até 60% do controle; os efeitos de silenciamento variaram de acordo com os alvos e doses. Os efeitos dos siRNA sobre a apoptose por neomicina foram determinados pelo ensaio de MTT. As células foram lesionadas por neomicina e tratadas com um dos siRNAs (exon2_hnNOS, exon28hnNOS ou scramble) por dois tempos distintos: imediatamente após ou 24h após a lesão. Ambas estruturas de siRNA mostraram efeitos antiapoptóticos, que alcançaram o máximo de 28,7%. Os efeitos variaram de acordo com o siRNA e o tempo de tratamento. Exon2_hnNOS produziu o maior efeito quando o tratamento foi realizado logo após lesão; exon28_hnNOS foi mais efetivo 24h após a lesão. Os resultados do atual estudo mostram a utilidade de siRNAs no entendimento da patogenia de doenças neurológicas e abrem novos caminhos para a terapia gênica de doenças neurodegenerativas.
Nitric oxide (NO) is formed by the NO synthase enzymes and play pivotal roles in the pathogenesis of neurodegenerative diseases. Neuronal NO synthase enzyme (nNOS) is expressed in brain areas submitted to injury, and its pharmacological blocking can decrease the effects of neurotoxic agents. In our study, we developed and tested two siRNAs targeted to two different nNOS mRNA sequences, located in the exons 2 and 28. Firstly, we used the Biopredsi algorithm to identify the RNAi targets. The synthetic siRNA duplexes with 21 nucleotides (exon2_hnNOS and exon28_hnNOS) were synthetized by Qiagen. Neuroblastoma cells SH-SY5Y received 150 pmol or 300 pmol of each siRNA mixed with Lipofectamine 2000® (Invitrogen). The negative control was the commercial scramble All-Stars® (Qiagen). The cell culture media used in this study were Optimen® and DMEM® (Gibco), for the first 6h and for the remaining 24h of incubation, respectively. The mRNA content was quantified by reverse transcription real-time PCR with SYBR Green® and the silencing effects on nNOS expressed by the relative expression (2-ΔΔCT). The nNOS mRNA content was reduced to 60% to the control level; the silencing effects varied according to the targets and doses used. To determine the effects of siRNA on the apoptotic phenotype, we used the MTT assay. Cells were lesioned by neomycin and treated with each of the siRNAs (exon2_hnNOS, exon28_hnNOS, or scramble) at two time-points: immediately after – or 24h after lesion. Both siRNA structures showed anti-apoptotic effects that reached 28.7%. The effects varied according to the siRNA used and the treatment time-point. Exon2_hnNOS produced the highest effect when the treatment began immediately after lesion; exon28_hnNOS was more effective 24h after lesion. Our results encourage the use of siRNAs to study the role of nNOS in the pathogenesis of brain diseases and highlighted a new therapeutic aproach for neurodegenerative diseases.
Balda, Mara A. "Ontogeny- and Sex-Dependent Contributions of the Neuronal Nitric Oxide Synthase (nNOS) Gene to Rewarding and Psychomotor Stimulating Effects of Cocaine." Scholarly Repository, 2009. http://scholarlyrepository.miami.edu/oa_dissertations/257.
Full textLustosa, Cátia Valderês dos Santos Faria. "Interferência de RNA para silenciamento gênico da enzima NO sintase neuronal (nNOS) no modelo in vitro de neurodegeneração por interferon gama." reponame:Repositório Institucional da UnB, 2013. http://repositorio.unb.br/handle/10482/13967.
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A vulnerabilidade de neurônios dopaminérgicos a insultos químicos continua sendo uma questão relevante na neuropatologia. Estudos anteriores revelam aumento dos níveis de interferon gama (IFN- ) e da enzima óxido nítrico sintase neuronal (nNOS) durante a injúria de células neuronais. Entretanto, até o momento, nenhum trabalho avaliou se a nNOS afeta a viabilidade de neurônios dopaminérgicos expostos ao IFN- . Para avaliar o papel da nNOS nas respostas celulares ao IFN- , o presente estudo realizou silenciamento gênico da enzima nNOS via interferência de RNA (RNAi) no modelo de neurodegeneração de células SH-SY5Y. Primeiro, analisou-se o conteúdo de RNAm de nNOS através de PCR em tempo real. Três RNAs interferentes sintéticos curtos foram testados nos tempos de 8h e 24h, em doses de 18,75nM e 37,5nM. Testou-se também um vetor de expressão de grampos curtos de RNA, denominado pnNOS_hum_4400 para o silenciamento da enzima. Os efeitos do silenciamento de nNOS sobre a viabilidade das células SH-SY5Y lesadas foram medidas via ensaio de 3-(4,5)-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT). O melhor efeito de silenciamento de nNOS ocorreu no tempo de 24h pós-transfecção para siRNAnNOShum_3987 e siRNAnNOShum_4400, com diminuição de 0,46 e 0,66 vezes. SiRNAnNOShum_4400 e o vetor pnNOS_hum_4400 aumentaram a viabilidade das células lesadas por IFN-y em 5,0 % e 15,8%, respectivamente. Conclui-se que a enzima nNOS participa de eventos celulares ligados à injúria de células SH-SY5Y causada pelo IFN- y. ______________________________________________________________________________ ABSTRACT
The vulnerability of dopaminergic neurons to chemical insults remains a relevant issue in neuropathology. Previous studies found increased levels of interferon gamma (IFN- ) and the neuronal nitric oxide synthase enzyme (nNOS) during neuronal injury. No previous work, however, has evaluated whether nNOS affects the viability of dopaminergic neurons exposed to IFN- . To gain more insight into the role of nNOS in cell responses to IFN- , the present study carried out the enzyme gene silencing by RNA interference (RNAi) in the neuron-like SH-SY5Y model of neurodegeneration. We first analyzed the nNOS mRNA knocking down by using a reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR). Three small interfering RNAs were tested at 8h and 24h in doses of 18.75nM and 37.5nM. We also tested a short-hairpin RNA expression vector named pnNOS_hum_4400 to improve enzyme knocking-down. nNOS silencing effects on the viability of injured SH-SY5Y cells were measured by the 3-(4,5)-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) assay. The highest knocking down in nNOS mRNA content occurred at 24h post-transfection for siRNAnNOShum_3987 and siRNAnNOShum_4400, with 0.46 and 0.66 fold decrease. SiRNAnNOShum_4400 and the vector pnNOS_hum_4400 ameliorate the viability of cells injured by IFN- 5,0 % 15,8 % ely. We concluded that nNOS enzyme plays at least a partial role in SH-SY5Y cell degeneration caused by IFN-y .
Silva, Maria Isabel. "Distribuição de celulas imunorreativas para sintase neuronal do oxido nitrico (nNOS) no hipocampo de pombos (Columba livia) apos aprendizagem de escolha alimentar." [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314142.
Full textDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: O hipocampo exerce papel fundamental no processamento de aprendizagem e memória espaciais. Comparações das características funcionais, anatômicas e neuroquímicas do hipocampo são favorecidas por evidência oriunda de estudo sobre aprendizagem especial em mamíferos e aves. O objetivo do presente estudo foi analisar a marcação imunohistoquímica de células nNOS- positivas no hipocampo de pombos (C. lívia) após diferentes duração do treino em aprendizagem especial. Foram analisados grupos de animais não treinados (MAN), treinados em 1 sessão (EXP1), treinados em 5 sessões (EXP5), exposto à arena em 1 sessão (CONT1) ou em 5 sessões (CONT5). As sessões foram realizadas numa arena onde havia quatro comedouros, um dos quais com alimento. Em cada sessão, com seis tentativas, registrou-se a latência (seg) e a assertividade da escolha de um comedouro. Após os testes comportamentais, usou-se imunoistoquímica para a análise da marcação de células nNOS-positiva no hipocampo dorsal e ventral. O grupo EXP5 teve diminuição da latência de escolha ('F IND. 4,28¿= 23,74; p < 0,001) e aumento das respostas corretas ('F IND. 4,35¿= 8,66; p < 0,001) em função do treino. A marcação das células nNOS-positivas no hipocampo foi significativamente maior no hipocampo dorsal dos animais EXP5 em comparação com o hipocampo ventral ('F IND. 4,22¿= 104,79; p<0,001) e com os demais grupos ('F IND. 4,22¿= 10,17; p < 0,001). O aumento da imunorratividade de células nNOS- positivas no hipocampo dorsal de pombos após a aprendizagem da localização do comedouro correto sugere o envolvimento desta região e de processos mediados pro transmissão glutamatérgica nesse processo de aprendizagem e memória em pombos
Abstract: The hippocampus has fundamental role in spatial learning and memory processes. Functional and neurochemical analysis of the hippocampus are favored by evidence on spatial learning in mammals and birds. The present study examined the immunohistochemical expression of nNOS-positive cells in the hippocampus of pigeons (C. livia) after training in food location task. Animals were trained in one (EXP1) or five (EXP5) sessions or had one (CONT1) or five sessions (CONT5) of exposure to the experimental arena. The six trials sessions were conducted daily in one arena with 4 food bowls, one of which had food. Latency and accuracy of choise recorded. After behavioral tests, nNOS immunoractivity in hippocampal cells was analyzed. EXP 5 showed reduction imunoreactivity in hippocampal cells was analysed. EXP5 showed reduction in latency of choise ('F IND. 4,28¿= 23,74; p < 0,001) and increassis in correct choise ('F IND. 4,35¿= 8,66; p < 0,001) as function of the training. The expression of nNOS- positive cells was significantily higher in the dorsal hippocampus of EXP5 group as compared with the ventral hippocampus ('F IND. 4,22¿= 104,79; p < 0,001) and the other groups ('F IND. 4,28¿= 10,17; p < 0,001). The increases of nNOS immunoreactive neurons after learning of the food location suggest that nNOS is involved in processes of spatial learning and memory that are mediated by the dorsal hippocampus of pigeons
Mestrado
Fisiologia
Mestre em Biologia Funcional e Molecular
Machado, Aline Vilar da Silva. "Variação circadiana da expressão da sintase neuronal de óxido nítrico (nNOS) no hipocampo e o condicionamento contextual aversivo em pombos (Columba livia)." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314744.
Full textDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: A ritmicidade circadiana, expressa na alteração do comportamento e em aspectos morfofisiológicos e moleculares ao longo das 24 horas do dia, é uma das funções básicas dos organismos vivos. Os processos comportamentais e os mecanismos moleculares no hipocampo, que estão envolvidos na aprendizagem e memória, demonstram oscilação circadiana. Vários estudos sugeriram que o condicionamento clássico aversivo é afetado pelo sistema de temporização circadiana e que a oscilação circadiana de vias moleculares específicas é requerida para a consolidação da memória aversiva. O presente trabalho investigou a oscilação circadiana da expressão da nNOS e da atividade da proteína NOS no hipocampo de pombos e as suas relações com a modulação temporal do condicionamento contextual aversivo. Na Parte I, caracterizou-se o padrão temporal da expressão da nNOS, que foi detectada por Western Blotting e o padrão temporal da atividade enzimática da NOS, determinada pela quantidade de L-citrulina produzida por minuto e por micrograma de proteína na reação. Na Parte II, nos horários de mínima e máxima atividade enzimática da proteína, pombos foram treinados e testados em condicionamento aversivo ao contexto. As sessões foram gravadas para posterior análise comportamental. Após o teste foi realizada a imunoistoquímica para marcação da nNOS em neurônios do hipocampo. Foi evidenciada ritmicidade circadiana significativa (p < 0,05) na expressão protéica da nNOS e na atividade enzimática da NOS, segundo os valores fornecidos pelo método Cosinor para caracterização do padrão temporal. As médias da densitometria óptica dos grupos com horários mais próximos da acrofase - ZT04 (10hs; 0,944 ± 0,12) e a batifase - ZT16-(22hs; 0,572 ± 0,16) foram significativamente diferentes (F5,18 p < 0,0001). Os grupos condicionados, em ambos os horários, mostraram maior duração e maior ocorrência do comportamento de congelamento do que os controles (p < 0,05). Houve uma variação dia-noite para o comportamento de congelamento nos grupos controles (p < 0,05). A marcação de células nNOS-positivas foi maior no hipocampo dos grupos condicionados sendo que o total de células nNOS-positivas na área dorsal do grupo experimental testado à noite foi maior do que aquele observado nos grupos controles e no experimental da manhã (p < 0,05). Os dados mostraram que a expressão protéica da nNOS e da atividade enzimática da NOS no hipocampo de pombos mostram uma oscilação que caracteriza um padrão temporal circadiano. Tanto no horário de máxima como no de mínima atividade da nNOS, o condicionamento contextual aversivo resultou em medo condicionado ao contexto e em expressão de células nNOS-positivas no hipocampo que foi maior nos pombos condicionados do que nos controles. Contudo, no hipocampo do grupo testado à noite houve um maior número de células nNOS-positivas. Esse dado estimula questionamento sobre se ocorreria a ativação de mecanismos compensatórios para o aumento da expressão da proteína nNOS, quanto essa é requisitada em situações de baixa disponibilidade
Abstract: The circadian rhythm, expressed in changing behavior and the morphophysiologic and molecular aspects over 24 hours of the day is one of the basic functions of living organisms. The behavioral processes and molecular mechanisms in the hippocampus, which are involved in learning and memory, show circadian oscillation. Several studies have suggested that classical fear conditioning is affected by the circadian timing system and the circadian oscillation of specific molecular pathways is required for the consolidation of aversive memory. This study investigated the circadian oscillation of nNOS expression and activity of NOS protein in the hippocampus of pigeons and their relationship with the temporal modulation of aversive contextual conditioning. In Part I, we have characterized the temporal pattern of nNOS expression, which was detected by Western blotting and temporal pattern of NOS enzyme activity, determined by the amount of L-citrulline produced per minute and per microgram of protein in the reaction. In Part II, at the times of minimum and maximum activity of the protein, pigeons were trained and tested in aversive conditioning to context. The sessions were taped for later behavioral analysis. After the test was performed immunohistochemical for labeling of nNOS in neurons in the hippocampus. Circadian rhythm was evident (p <0.05) in nNOS protein expression and enzyme activity of NOS, according to figures provided by Cosinor method to characterize the temporal pattern. The mean optical density of groups with times closer to the acrophase - ZT04 (10hrs; 0.944 ± 0.12) and nadir - ZT16-(22hs; 0.572 ± 0.16) were significantly different (F5, 18 p <0.0001 ). The groups conditioned in both schedules, showed more frequent and longer duration of freezing behavior than controls (p <0.05). There was a day-night variation for freezing behavior in control groups (p <0.05). Labeling of nNOS-positive cells was higher in the hippocampus of the groups conditioned with total nNOS-positive cells in the dorsal area of the experimental group tested at night was higher than that observed in control groups and experimental group in the morning (p <0.05). The data showed that nNOS protein expression and enzymatic activity of NOS in the hippocampus of pigeons show an oscillation that characterizes a circadian temporal pattern. Both at the time of maximum as the low activity of nNOS, the aversive contextual conditioning resulted in fear conditioning to context and expression of nNOS-positive cells in the hippocampus was higher in pigeons conditioned than in controls. However, in the hippocampus of the group tested in the evening there was a greater number of nNOS-positive cells. This fact encourages questioning of whether there would be activation of compensatory mechanisms for the increased expression of nNOS protein, as this is required in situations of low availability
Mestrado
Fisiologia
Mestre em Biologia Funcional e Molecular
Faria, Larissa Oliveira Melloni de 1985. "Participação da sintase neuronal de óxido nítrico (nNOS) na consolidação e reconsolidação da memória do condicionamento clássico aversivo em pombos (Columba livia)." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314128.
Full textDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-08-23T06:24:39Z (GMT). No. of bitstreams: 1 Faria_LarissaOliveiraMellonide_M.pdf: 1121073 bytes, checksum: 5a3108ca0447b5fae98988b4611d7616 (MD5) Previous issue date: 2013
Resumo: O óxido nítrico (NO) é um neurotransmissor não convencional o qual tem papel importante em processos neurobiológicos de comportamento e de memória. Sua síntese é mediada por três isoformas de sintase do óxido nítrico (NOS): a neuronal (nNOS), a endotelial (eNOS) e a induzível (iNOS). Este trabalho investigou os efeitos da administração do 7- nitroindazol (7-NI), inibidor preferencial da nNOS, na consolidação e reconsolidação da memória do condicionamento clássico aversivo. Pombos adultos foram atribuídos a 5 grupos: Foram usados 5 grupos: grupo 7-nitroindazole (7-NI) (100nmol/0.5?/l; DMSO (20%), NaOH (50mM) e Tween-80 (16%) diluído em PBS; i.c.v.), grupo veículo (VEIC) (0,5?/l; DMSO (20%), NaOH (50mM) e Tween-80 (16%) diluído em PBS, i.c.v.), grupo condicionado/não tratado (COND), grupo contexto/não-tratado (CONT) e grupo não tratado/não condicionado (NÄIVE). Sete dias após implante de microcânula intracerebroventricular (i.c.v.), ocorreu o condicionamento com três associações contextochoque numa sessão de 20 min. O teste e o re-teste consistiram na re-exposição ao contexto do condicionamento por 5 min. O intervalo entre sessões foi de 24h. A administração de 7-NI ou do veículo ocorreu imediatamente após o treino (Experimento 1) ou após o re-teste (Experimento 2). A atividade enzimática da NOS dependente e independente de Ca2+ e da expressão protéica da nNOS foram realizadas no tecido hipocampal. No Experimento 1, a ocorrência de congelamento no teste do 7-NI foi menor do que no treino (p<0.01) e no teste do COND e VEIC (p < 0.001). A atividade da NOS dependente de Ca++ no 7-NI foi menor do que no COND e VEIC (p<0,01), mas não diferiu do CONT e do NÄIVE. A expressão protéica de nNOS não diferiu entre os grupos (p<0,05). No Experimento 2, houve diminuição dos comportamentos defensivos, incluindo o congelamento, no re-teste do 7-NI comparado com VEIC e COND (p<0.05), mas os grupos não diferiram quanto à atividade de NOS dependente de Ca2+ ou à expressão protéica da nNOS. Conclui-se que o 7-NI interferiu na consolidação e a reconsolidação da memória, indicando a ativação da via de sinalização do óxido nítrico no hipocampo em processos da memória de medo condicionado ao contexto em pombos
Abstract: Nitric oxide (NO) is an unconventional neurotransmitter which plays an important role in neurobiological processes of behavior and memory. Its synthesis is mediated by three isoforms of nitric oxide synthase (NOS): the neuronal (nNOS), the endothelial (eNOS) and the inducible (iNOS). This study investigated the effects of the administration of 7- nitroindazole (7-NI), a preferential nNOS inhibitor, in the consolidation and reconsolidation of aversive classical conditioning memory. Adult male pigeons were assigned to 5 groups: 7-nitroindazole, 7-NI (100nmol/0.5?/l; DMSO (20%), NaOH (50 mM) and Tween-80 (16%) diluted in PBS; i.c.v.) Vehicle group; VEH (0.5 ? / L; DMSO (20%), NaOH (50 mM) and Tween-80 (16%) diluted in PBS; i.c.v.), conditioning/non-treated group (COND), context/non-treated group (CONT) and non-conditioning/non-treated group (NÄIVE). Seven days after implantation of intracerebral ventricular (i.c.v.) microcannula the conditioning occurred with three context-shock associations in a session of 20 min. During the testing and retesting sessions pigeons were reexposed to the conditioning context for 5 min. The between sessions interval was 24h. Administration of 7-NI or vehicle occurred immediately after training (Experiment 1) or after testing (Experiment 2). The enzymatic activity of Ca2+ dependent and independent NOS and protein expression of nNOS in the hippocampus tissue were carried out following the behavioral test or retest. In Experiment 1, the occurrence of freezing in the testing session of 7-NI group was lower than in the training (p <0.01) and the testing sessions of COND and VEH groups (p <0.001). The activity of Ca2+ dependent NOS in the 7-NI group was lower than in COND and VEH groups (p <0.01) but did not differ from CONT and NÄIVE groups. The nNOS protein expression in the hippocampus did not differ among the different groups (p<0.05). In Experiment 2, there was a decrease of defensive behaviors, which include freezing, in the retest of the 7-NI compared with VEH and COND groups (p <0.05), but the groups did not differ in the activity of Ca2+ dependent NOS or the protein expression of nNOS. We conclude that 7-NI interfered on the consolidation and reconsolidation of memory, indicating activation of the nitric oxide signaling pathway in the hippocampus and in memory processes of conditioned fear context in pigeons
Mestrado
Fisiologia
Mestra em Biologia Funcional e Molecular
Luis, Delgado Oliva Erendira. "Etude de l'induction de DeltaFosB dans la moëlle épinière lors d'une stimulation nociceptive de type inflammatoire et de ses relations avec nNOS." Université Louis Pasteur (Strasbourg) (1971-2008), 2006. https://publication-theses.unistra.fr/public/theses_doctorat/2006/LUIS_DELGADO_Oliva_Erendira_2006.pdf.
Full textDezengrini, Renata. "HERPESVÍRUS BOVINO TIPOS 1, 2 E 5: SENSIBILIDADE A ANTIVIRAIS IN VITRO, PATOGENIA E TERAPÊUTICA EXPERIMENTAL EM COELHOS." Universidade Federal de Santa Maria, 2009. http://repositorio.ufsm.br/handle/1/4039.
Full textAspects of bovine herpesvirus 5 (BoHV-5) pathogenesis and experimental therapies against BoHV-1 and BoHV-5 were investigated in vitro and in inoculated rabbits. In chapter 1, we investigated the role of nitric oxide (NO), a component of innate immunity against pathogens, in the neurological disease by BoHV-5 in rabbits. Spectrophotometry for NO products revealed that NO levels were significantly increased in several regions of the brain of rabbits with neurological disease [F(4, 40)=3.33; P<0.02]. Quantification of NO levels in the brain at different time points after virus inoculation revealed a gradual increase [F(12, 128)=2.82; P<0,003], correlated spatially and temporally with virus dissemination within the brain and preceding the development of neurological signs. Thus, we propose that the overproduction of NO in the brain of BoHV-5-infected rabbits may participate in the pathogenesis of neurological disease. In chapter 2, the activity of three anti-herpetic drugs was tested against BoHV-1, BoHV-2 and BoHV-5 in vitro by plaque reduction assay. Acyclovir was moderately active against the three viruses; Gancyclovir was moderately effective against BoHV-2, and to a lesser extent against BoHV-5, being poorly active against BoHV-1. Foscarnet (PFA) exhibited the most pronounced antiviral activity, being the only drug that, at the concentration of 100 ìg/mL, completely inhibited plaque formation by all three viruses. In chapter 3, we report the activity of PFA in rabbits inoculated with BoHV-1 or BoHV-5. Rabbits inoculated with BoHV-5 and treated with 100 mg/kg of PFA presented mortality rates (11/22 or 50%) statistically lower than non-treated controls (21/22 ou 95.4%) (P<0.0008). A significant reduction in the mean virus titers was observed at day 3 pi, the peak of virus shedding [F(9,108) = 2,23; P<0.03]. Reduction in virus shedding, frequency, severity and duration of ocular signs were also observed in rabbits inoculated with BoHV-1 into the conjunctival sac, comparing to the controls. The prolonged incubation period and the reduction in the duration of the clinical course of the PFA-treated group was significant (P<0.005 and P<0.04, respectively). Therefore, the activity of PFA in vivo against BoHV-1 and BoHV-5 may be exploited in further experimental therapies. In chapter 4, we investigated the effect of the inhibition of the inducible isoform of nitric oxide synthase (iNOS), associated or not with PFA treatment, on neurological infection by BoHV-5 in rabbits. Groups of BoHV-5-inoculated rabbits were treated with the iNOS inhibitor aminoguanidine (AG); with PFA; with both drugs; or maintained as virus controls. Morbidity and mortality rates were 100% (6/6) in the groups AG and CV, 66.7% (4/6) in the group PFA and 83.3% (5/6) in the group AG+PFA. The incubation period was significantly lower (P<0.05) and the onset of neurological disease occurred earlier and was more severe in the group AG. These results demonstrate that treatment with PFA reduced morbidity and mortality rates associated to BoHV-5 infection, that AG treatment anticipated the development of neurological signs, and that the development of neurolocial disease was delayed in the group treated with both drugs. Taken together, these results contribute to the knowledge of the pathogenesis of BoHV-5 neurological disease and pave the way for other experimental pathogenesis and therapy studies.
Aspectos da patogenia da infecção neurológica pelo herpesvírus bovino 5 (BoHV-5) e terapias experimentais contra o BoHV-1 e BoHV-5 foram estudados in vitro e em coelhos inoculados. O capítulo 1 relata a investigação do papel do óxido nítrico (NO), um componente da imunidade inata contra patógenos, na doença neurológica produzida pelo BoHV-5 em coelhos. Espectrofotometria para os produtos de degradação do NO revelou um aumento significativo nos seus níveis em várias regiões do encéfalo de coelhos infectados (F(4, 40)=3.33; P<0,02). A quantificação do NO no encéfalo nos dias seguintes à inoculação viral revelou um aumento gradativo (F(12, 128)=2.82; P<0,003), correlacionado temporal e espacialmente com a invasão e disseminação viral, e precedendo o desenvolvimento de sinais neurológicos. Sugere-se, assim, que a produção aumentada de NO em resposta à infecção possa participar da patogenia dessa doença neurológica. No capítulo 2, investigou-se a atividade de três fármacos antivirais frente ao BoHV-1, BoHV-2 e BoHV-5 in vitro pelo teste de redução do número de placas. O Aciclovir foi moderadamente ativo frente aos três vírus; o Ganciclovir apresentou atividade moderada frente ao BoHV-2 e, em menor grau, contra o BoHV-5, sendo ineficaz frente ao BoHV-1. O Foscarnet (PFA) apresentou a atividade antiviral mais pronunciada, sendo o único fármaco que, na concentração de 100 μg/mL, inibiu completamente a produção de placas pelos três herpesvírus bovinos. No capítulo 3, investigou-se a atividade do PFA em coelhos inoculados com o BoHV-1 ou BoHV-5. Coelhos inoculados com o BoHV-5 e tratados com 100 mg/kg do PFA apresentaram índices de mortalidade (11/22; 50%) estatisticamente inferiores aos controles não-tratados (21/22; 93,7%) (P<0,0008). Uma redução significativa no título médio de vírus foi observada no dia 3 pi, pico da excreção viral [F(9,108) = 2,23; P<0,03]. Em coelhos inoculados no saco conjuntival com o BoHV-1 e tratados com o PFA, foram observadas reduções na excreção viral, na frequência, severidade comparando-se com o grupo controle. O período de incubação prolongado e a redução na duração do curso clínico no grupo tratado foi significante (P<0,005 e P<0,04, respectivamente). A atividade antiviral do PFA in vivo contra o BoHV-1 e BoHV-5 abre a perspectiva para outras terapias experimentais. No capítulo 4, investigou-se o efeito da inibição da isoforma induzível da enzima óxido nítrico sintase (iNOS), associada ou não ao tratamento com o PFA, na infecção neurológica pelo BoHV-5 em coelhos. Grupos de coelhos inoculados com o BoHV-5 foram tratados com o inibidor da iNOS aminoguanidina (AG); com PFA; com ambos os fármacos; ou não receberam tratamento. Os índices de morbidade e mortalidade foram de 100% (6/6) nos grupos AG e controle; 66,7% (4/6) no grupo PFA e 83,3% (5/6) no grupo AG+PFA. O período de incubação foi significativamente menor (P<0,05) e os sinais neurológicos foram mais precoces e severos nos animais do grupo AG. Portanto, o tratamento com PFA reduziu a morbidade e mortalidade associadas com a infecção pelo BoHV-5; o tratamento com AG resultou no agravamento e na antecipação do quadro neurológico e no grupo tratado com ambos os fármacos observou-se um desenvolvimento mais tardio dos sinais neurológicos. Esses resultados contribuem para o conhecimento da patogenia da doença neurológica pelo BoHV-5 e abrem perspectivas para estudos adicionais de patogenia e terapêutica anti-herpesvírus.
Pierson, Shawn M. "Aspects of the transcriptional and translational regulation of nitric oxide synthase 1." Connect to this title online, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1111595828.
Full textTitle from first page of PDF file. Document formatted into pages; contains x, 156 p.; also includes graphics (some col.) Includes bibliographical references (p. 146-156). Available online via OhioLINK's ETD Center
Moszkowicz, David. "Etude anatomique et fonctionnelle de l'innervation pelvipérinéale de la femme : cartographie tridimensionnelle de l'expression de la forme neurale de l'enzyme de synthèse de l'oxyde nitrique (nNOS)." Phd thesis, Université Paris Sud - Paris XI, 2012. http://tel.archives-ouvertes.fr/tel-00775860.
Full textMoszkowicz, David. "Etude anatomique et fonctionnelle de l’innervation pelvipérinéale de la femme : cartographie tridimensionnelle de l’expression de la forme neurale de l’enzyme de synthèse de l’oxyde nitrique (nNOS)." Thesis, Paris 11, 2012. http://www.theses.fr/2012PA114836/document.
Full textAnatomical knowledge is required for the development of surgical techniques,but little is known about the anatomy and physiology of innervation in the pelvic/perinealarea. The origin, perivisceral trajectory, anatomical relationships to organs and neighbouringvessels and of the endings of these nerves in the organs they control has not, to date, beeneasy to determine precisely by classical anatomical techniques based on the macroscopicdissection of cadavers. In the domain of pelvic cancer surgery, improvements in the quality oflife of patients are dependent on the preservation of these nervous system structures; themaintenance of function cannot be dissociated from oncological imperatives. Indeed, theintegrity of these nerves is essential for sphincter continence and sexual functions. Moststudies have focused on the functional sequelae of surgery in men. Very few studies havefocused exclusively on women, in whom sexual problems are more difficult to identify. Thereduction of such postsurgical functional problems thus requires a more completeunderstanding of the anatomy of the pelvic/perineal nervous system. This may be possiblethrough the use of new investigative techniques
Jurzik, Lars. "Veränderung der neuronalen Vasoregulation im mesenterialen Gefässbett bei portaler Hypertension mit besonderem Fokus auf die neuronale Stickstoffmonoxyd-Synthase (nNOS)-vermittelte Vasorelaxation und die Neuropeptid-Y-(NPY)-induzierte Vasokonstriktion /." [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=973326840.
Full textTajouri, Lotfi, and n/a. "Gene Expression Analysis and Genetic Studies in Multiple Sclerosis." Griffith University. School of Health Science, 2005. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20060111.123933.
Full textTajouri, Lotfi. "Gene Expression Analysis and Genetic Studies in Multiple Sclerosis." Thesis, Griffith University, 2005. http://hdl.handle.net/10072/366467.
Full textThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Health Sciences
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van, Erp Christel. "Modifying function and fibrosis of cardiac and skeletal muscle from mdx mice." University of Southern Queensland, Faculty of Sciences, 2005. http://eprints.usq.edu.au/archive/00001521/.
Full textChachlaki, Konstantina. "Molecular characterization of NO-synthesizing neurons and assessment of their function in the maturation of the hypothalamic - pituitary - gonadal axis." Thesis, Lille 2, 2016. http://www.theses.fr/2016LIL2S047.
Full textThe onset of puberty and the regulation of fertility in mammals are governed by a complex neural network, primarily in the hypothalamus, that converges onto gonadotropin-releasing hormone (GnRH)-producing neurons, the master regulators of gonadotropin secretion and postnatal gonadal growth and function. The proper development of the GnRH system, including timely changes in GnRH expression and signaling by this sparse population of a few hundred neurons, is essential for sexual maturation and the normal functioning of the hypothalamic-pituitary-gonadal axis. As the brain develops during embryogenesis, these neurons should move from the olfactory placode into the correct brain location in adequate numbers, and then establish the afferent connections that will allow the pulsatile release of GnRH peptide, and the subsequent release of the gonadotropins (follicle stimulating hormone, i.e FSH and luteinizing hormone, ie. LH). As early as in the 90’s NO was presented as a key molecule in the preovulatory GnRH/LH surge, and results from different groups, have suggested the interaction of NOS-containing neurons with the GnRH system, and their involvement in the regulation of reproductive capacity. Even though nitric oxide has now been long recognized as a key player in the central hormonal regulation of ovulation during adulthood, no one has considered the possibility that it could act in an earlier stage as the master regulator of GnRH neurons before puberty, hence participating in the actual maturation of the neuroendocrine axis. The relationship of nNOS-expressing neurons with other important molecules of the hypothalamic axis has been well studied, whilst the molecular identity of this neuronal NOS-expressing population is poorly documented. . To this end, we address the hitherto unaddressed questions concerning 1) the molecular identity of nNOS-expressing neurons in the developing hypothalamus, 2) the putative involvement of the NO molecule in the migration of GnRH neurons and the proper establishment of their afferent connections in the hypothalamic region and 3) the plausible determinant role of NO signaling in the maturation of the reproductive system. During this study we identified for the first time the cohort of the principal neurotransmitters and important receptors expressed by these cells in the hypothalamic region during development. Additionally, our results reveal for the first time an involvement of NO signaling in the migration of GnRH neurons in the hypothalamus and are in line with the identification of a series of NOS1 mutations in Kallmann syndrome (KS), a rare congenital genetic condition presenting a unique combination of GnRH deficiency, arising from a faulty migration of the neuronal population, and anosmia. Lastly, our study identifies NO as a novel protagonist during postnatal development, in the regulation of the onset of puberty and the acquisition of reproductive competence. Overall, the results of my Phd thesis identify putative new targets causing alterations of developmental programming under pathophysiological gestational environment in mammals in general, and in humans in particular. Here we thus provide new insights into the mechanisms by which the alteration of GnRH neuronal function leads to hypogonadotropic hypogonadism and infertility. We are hopeful that our results will expand our understanding of how the neuroendocrine axis is regulated and will possibly provide opportunities for therapeutic strategies against debilitating conditions
Barreiro, Portela Esther. "Study of reactive oxygen species (ROS) and nitric oxide (NO) as molecular mediators of the sepsis-induced diaphragmatic contractile dysfunction : protective effect of heme oxygenases." Doctoral thesis, Universitat Pompeu Fabra, 2002. http://hdl.handle.net/10803/7066.
Full textEn un model de sepsi de disfunció diafragmàtica, s´ha avaluat el paper de les sintetases de l'òxid nítric (NOS) en la formació i localitzacio de 3-nitrotirosina, i l´expressió i significat biològic de les hemo oxigenases (HOs) (inhibidor de les HOs i estudis de contractilitat) davant l' estrès oxidatiu. La sepsi s'induí mitjançant injecció de 20 mg/kg del lipolisacàrid (LPS) d´Escherichia Coli a rates, i a ratolins deficients en les NOS induïble (iNOS), neuronal (nNOS) i endotelial (eNOS). Les proteïnes nitrificades i les HOs es van detectar amb anticossos específics. L' estrès oxidatiu s' avaluà mitjançant l' oxidació proteica, la peroxidació lipídica i el glutation muscular. Concloem que hi han proteïnes nitrificades en el múscul normal i aquestes s'incrementen durant la sepsi en les fraccions mitocondrial i membranar. L'isoforma iNOS és majorment responsable de la formació de nitrotirosina. Les HOs protegirien el múscul normal i sèptic dels efectes deleteris dels oxidants.
Guilbaud, Marine. "Identification d'ARNs non-codants impliqués dans les dystrophinopathies." Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUS042/document.
Full textDuchenne (DMD) and Becker (BMD) muscular dystrophies are due to mutations in DMD gene, encoding Dystrophin. Many aspects of pathophysiological mechanisms of these diseases are not yet well understood. We were interested in the study of non-coding RNAs that could be involved in these pathological processes. A first study focused on micro-RNAs (miRNAs) that could modulate expression of the neuronal nitric oxide synthase (nNOS), a partner of Dystrophin which is linked to pathological features as muscular fatigability. 617 miRNAs were screened by Taqman Low Density Array in muscle biopsies of healthy subjects or BMDdel45-55 patients. 4 candidate miRNAs were selected from this study since they were overexpressed in BMDdel45-55 patients and for their theoretical ability to target nNOS. Experiments modulating the expression of these miRNAs in healthy or dystrophic human myoblasts enabled us to identify that miR-708-5p and miR-34-5p could target nNOS and modulate its expression.A second axis was conducted on long non-coding RNA (lncRNA). Introns 44 and 55, which bound exons 45-55 deleted in BMDdel45-55 patients, are large regions containing lncRNAs described as regulating Dystrophin. Since intronic breakpoints of DMD mutations of these pateints were not described, we have assumed the existence of different profiles of lncRNAs. DNA analysis of these patients actually showed different lncRNAs profiles, thus revealing the significance of a more precise analysis of deletion areas in DMD gene of BMDdel45-55 patients
Khadrah, S. "NNS/NNS interaction during task-based synchronous computer-mediated communication." Thesis, University of Manchester, 2007. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.508026.
Full textBezerra, Paulo Cesar Rego, and Jose Bittencourt de 1937 Andrade. "Sistemas de referencia associados ao NNSS." reponame:Repositório Institucional da UFPR, 2013. http://hdl.handle.net/1884/32062.
Full textIwashita, Noriko. "Comprehensible output in NNS-NNS interaction in Japanese as a foreign language." Connect to thesis, 1993. http://repository.unimelb.edu.au/10187/1523.
Full textThe results show that comprehensible output is an important phenomenon in NNS-NNS interaction. Unlike the result of Pica et al, task types had more effect on opportunities for comprehensible output and actual production of comprehensible output than request types. Not much difference was found among different proficiency groups.
Faiglová, Veronika. "Posouzení faktorů úspěšnosti NNO." Master's thesis, Vysoká škola ekonomická v Praze, 2008. http://www.nusl.cz/ntk/nusl-10632.
Full textManley, Lucy B. "Embedding the Consultant: A NNES Case Study." Miami University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=miami1407853148.
Full textKorený, Jozef. "Faktory efektivity rozvojových programů NNO." Master's thesis, Vysoká škola ekonomická v Praze, 2007. http://www.nusl.cz/ntk/nusl-1011.
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