582 resultados para GABA-A


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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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In birds, neurons of the isthmo-optic nucleus (ION), as well as ''ectopic'' neurons, send axons to the retina, where they synapse on cells in the inner nuclear layer (INL). Previous work has shown that centrifugal axons can be divided into two anatomically distinct types depending on their mode of termination: either ''convergent'' or ''divergent'' (Ramon y Cajal, 1889; Maturana and Frenk, 1965). We show that cytochrome-oxidase histochemistry specifically labels ''convergent'' centrifugal axons and target neurons which appear to be amacrine cells, as well as three ''types'' of ganglion cells: two types found in the INL (displaced ganglion cells) and one in the ganglion cell layer. Labeled target amacrine cells have distinct darkly labeled ''nests'' of boutons enveloping the somas, are associated with labeled centrifugal fibers, and are confined to central retina. Lesions of the isthmo-optic tract abolish the cytochrome-oxidase labeling in the centrifugal axons and in the target amacrine cells but not in the ganglion cells. Cytochromeoxidase-labeled ganglion cells in the INL are large; one type is oval and similar to the classical displaced ganglion cells of Dogiel, which have been reported to receive centrifugal input; the other type is rounder. Rhodamine beads injected into the accessory optic system results in retrograde label in both types of cells, showing that two distinct types of displaced ganglion cells project to the accessory optic system in chickens. The ganglion cells in the ganglion cell layer that label for cytochrome oxidase also project to the accessory optic system. These have proximal dendrites that ramify in the outer inner plexiform layer. Neither the target amacrine cells nor either of the displaced ganglion cells are immunoreactive for the inhibitory transmitter gamma aminobutyric acid. At least some of the target amacrine cells may, however, be cholinoceptive: we found that the antibody to the alpha-7 subunit of the nicotinic ACh receptor labels a population of cells in the INL that are similar in location, size, and the presence of labeled bouton-like structures to those we find labeled with cytochrome oxidase. This antibody also labels neurons in the ION proper but not ectopic cells. In conclusion, it appears that cytochrome oxidase may be a marker for ''convergent'' centrifugal axons and at least one of their target cells in the INL.

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O núcleo parabraquial lateral (NPBL) e o núcleo Kölliker-Fuse (KF) são os mais importantes núcleos da ponte envolvidos com o controle da ventilação pulmonar (VE) e são conhecidos como grupo respiratório pontino ou centro pneumotáxico. Vários experimentos demonstraram que a estimulação ou a lesão do NPBL-KF produziram alterações nos padrões respiratórios. No entanto, ainda não estava claro qual seria a área exata (no complexo NPBL-KF) e o neurotransmissor envolvido nas alterações respiratórias. Estudos com imunohistoquímica demonstraram a presença de receptores purinérgicos (especialmente os P2X) em várias áreas envolvidas com o controle da ventilação, incluindo o NPBL. Estudos também demonstraram a presença de um denso plexo de varicosidades imunorreativas para o GABA ao longo do complexo NPB-KF, sendo que o processamento neural nessa região estaria sob forte inibição gabaérgica. No entanto, o papel dos receptores purinérgicos e gabaérgicos do NPBL na regulação da VE em ratos não anestesiados ainda não tinha sido investigado. Desta forma, no presente estudo investigamos as respostas ventilatórias após a injeção do α,β-metil-ATP (agonista purinérgico), do PPADS (antagonista purinérgico) e do muscimol (agonista GABA-A) no NPBL de ratos não anestesiados. Foram utilizados ratos com cânulas de aço inoxidável bilateralmente no NPBL, os animais foram submetidos a pletismografia de corpo inteiro para que fossem obtidas as medidas de VE. As injeções bilaterais do agonista purinérgico, α,β-metil-ATP (2 nmol/0,2 μl, n=8), no NPBL promoveu queda na freqüência respiratória (fR) (108  5 ciclos/min vs basal 137  6 ciclos/min, p = 0,005), não alterou o volume corrente (VT) (2  0,3 ml/kg vs basal 2  0,3 ml/kg, p = 0,967) e queda na VE (263  42 ml.kg-1.min-1 vs basal 325  43 ml.kg-1.min-1, p = 0,001)... (Resumo completo, clicar acesso eletrônico abaixo)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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A epilepsia é a doença neurológica maiscomum em seres humanos e cães, possui diversas etiologias e é classificada em epilepsia primária, idiopática ou hereditária e epilepsia secundária ou adquirida. A maioria dos cães epiléticos é tratada com fármacos antiepiléticos padrões, fenobarbital e/ou brometo de potássio, com os quais obtém-se sucesso; porém, cerca de 20-30% dos cães tratados necessitam de terapia adicional, pois não respondem a terapia padrão. Os medicamentos utilizados como anticonvulsivantes levam a efeitos de toxicidade e menos de 50% dos cães com epilepsia permanecem livres de convulsões sem efeitos secundários das medicações. Novas alternativas terapêuticas têm sido utilizadas. Dentre elas, a Gabapentina que é um medicamento análogo ao GABA e possui diferentes mecanismos de ação, tem efeito dose-dependente, absorção saturada, não tem ligação às proteínas plasmáticas e, ao contrário da maioria das medicações anticonvulsivas, possui eliminação renal. Quando sua eficácia é comprovada em associação às drogas anticonvulsivas padrões, é possível a redução da dose das mesmas evitando ou minimizando assim os desagradáveis efeitos secundários destas medicações. Por esses motivos, o objetivo desse trabalho é averiguar a eficácia da Gabapentina quando associada aos fármacos padrões utilizados na terapia antiepilética. Para tanto, foi realizado um levantamento bibliográfico em cinco bases de dados eletrônicos. Foram obtidos 13 artigos, os quais, após serem analisados, permitiram concluir que a Gabapentina apresenta resultados significativamente satisfatórios no tratamento da epilepsia idiopática em cães refratários ao tratamento padrão; porém, mais estudos em cães não devem ser descartados de modo a melhor elucidar esses efeitos

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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We examined the effects of beta-pompilidotoxin (beta-PMTX), a neurotoxin derived from wasp venom. on synaptic transmission in the mammalian central nervous system (CNS). Using hippocampal slice preparations of rodents, we made both extracellular and intracellular recordings from the CA1 pyramidal neurons in response to stimulation of the Schaffer collateral/commissural fibers. Application of 5-10 muM beta-PMTX enhanced excitatory postsynaptic potentials (EPSPs) but suppressed the fast component of the inhibitory postsynaptic potentials (IPSPs). In the presence of 10 muM bicuculline, beta-PMTX potentiated EPSPs that were composed of both non-NMDA and NMDA receptor-mediated potentials. Potentiation of EPSPs was originated by repetitive firings of the prosynaptic axons, causing Summation of EPSPs. In the presence of 10 muM CNQX and 50 muM APV, beta-PMTX suppressed GABA(A) receptor-mediated fast IPSPs but retained GABA(B) receptor-mediated slow IPSPs. Our results suggest that beta-PMTX facilitates excitatory synaptic transmission by a presynaptic mechanism and that it causes overexcitation followed by block of the activity of some population of interneurons which regulate the activity of GABA(A) receptors. (C) 2001 Published by Elsevier B.V. Ireland Ltd and the Japan Neuroscience Society.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Stress is an environmental factor that may predispose individuals to depression. Benzodiazepines have been prescribed as effective drugs in these situations. The purpose of this study was histological evaluate of the effect of chronic stress and benzodiazepine drugs on bone healing. Bone cavities were created in both tibias of 40 male rats were divided into two groups: Control and Treaty. In this, the stressor stimulus was applied 40 days pre-operative and all post-operative days until sacrifice in the morning for 2 hours, by immobilizing restraint. These animals also received diazepam benzodiazepine group, daily, at a concentration of 5mg/Kg/peso body within 15 days of preoperative. In groups of five animals were sacrificed at 7, 14, 30 and 60 days post-surgery. At 7 days postoperatively, while the control group exhibited tissue rich in fibroblasts, the treated group showed newly formed tissue with few fibroblasts and capillaries along with lymphocytes and macrophages. At 14 days postsurgery, the control group showed newly formed trabecular bone while the treated group progressed to thin trabecular bone with numerous osteoblasts on their borders. At 30 days post-operative bone healing is complete in both groups. At 60 days post-operative characteristics observed in the treated and control groups are similar to the previous period, but with more advanced osteogenesis.

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Pós-graduação em Ciências Biológicas (Farmacologia) - IBB

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Objective: The aim of this study is to investigate the effects of pregabalin on the behavior of rats under the influence of ketamine, an NMDA receptor antagonist that mimics the symptoms of schizophrenia. Methods: Rats were injected with saline or 25 mg/kg ketamine intraperitoneally. After that, behavior modifications were investigated by the evaluation of stereotypy and hyperlocomotion, after treating rats with pregabalin (at doses of 30 mg/kg or 100 mg/kg) or placebo (saline solution). Results: The administration of pregabalin reduced ketamine-induced hyperlocomotion. However, neither doses of pregabalin had a significant effect on ketamine-induced stereotypy. Conclusion: This is the first study to investigate the effects of pregabalin using an animal model of psychosis. Furthermore, our results indicate that behavioral changes induced by ketamine in rats can be reversed with the use of pregabalin, suggesting its potential to treat psychotic symptoms.

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During exercise, intense brain activity orchestrates an increase in muscle tension. Additionally, there is an increase in cardiac output and ventilation to compensate the increased metabolic demand of muscle activity and to facilitate the removal of CO2 from and the delivery of O-2 to tissues. Here we tested the hypothesis that a subset of pontomedullary and hypothalamic neurons could be activated during dynamic acute exercise. Male Wistar rats (250-350 g) were divided into an exercise group (n = 12) that ran on a treadmill and a no-exercise group (n = 7). Immunohistochemistry of pontomedullary and hypothalamic sections to identify activation (c-Fos expression) of cardiorespiratory areas showed that the no-exercise rats exhibited minimal Fos expression. In contrast, there was intense activation of the nucleus of the solitary tract, the ventrolateral medulla (including the presumed central chemoreceptor neurons in the retrotrapezoid/parafacial region), the lateral parabrachial nucleus, the Kolliker-Fuse region, the perifornical region, which includes the perifornical area and the lateral hypothalamus, the dorsal medial hypothalamus, and the paraventricular nucleus of the hypothalamus after running exercise. Additionally, we observed Fos immunoreactivity in catecholaminergic neurons within the ventrolateral medulla (C1 region) without Fos expression in the A2, A5 and A7 neurons. In summary, we show for the first time that after acute exercise there is an intense activation of brain areas crucial for cardiorespiratory control. Possible involvement of the central command mechanism should be considered. Our results suggest whole brain-specific mobilization to correct and compensate the homeostatic changes produced by acute exercise. (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

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Systemic injection of pilocarpine in rodents induces status epilepticus (SE) and reproduces the main characteristics of temporal lobe epilepsy (TLE). Different mechanisms are activated by SE contributing to cell death and immune system activation. We used BALB/c nude mice, a mutant that is severely immunocompromised, to characterize seizure pattern, neurochemical changes, cell death and c-Fos activation secondarily to pilocarpine-induced SE. The behavioral seizures were less severe in BALB/c nude than in BALB/c wild type mice. However, nude mice presented more tonic clonic episodes and higher mortality rate during SE. The c-Fos expression was most prominent in the caudate-putamen, CA3 (p < 0.05), dentate gyrus, entorhinal cortex (p < 0.001), basolateral nucleus of amygdala (p < 0.01) and piriform cortex (p < 0.05) of BALB/c nude mice than of BALB/c. Besides, nude mice subjected to SE presented high number of Fluorojade-B (FJB) stained cells in the piriform cortex, amygdala (p < 0.05) and hilus (p < 0.05) in comparison with BALB/c mice. A significant increase in the level of glutamate and GABA was found in the hippocampus and cortex of BALB/c mice presenting SE in comparison to controls. However, the level of glutamate was higher in the brains of BALB nude mice than in the brains of BALB/c wild type mice, while the levels of GABA were unchanged. These results indicate that the brains of immunodeficient nude mice are more vulnerable to the deleterious effects of pilocarpine-induced SE as they present intense activation, increased glutamate levels and more cell death. Published by Elsevier B.V.