Search results for "GABA"
showing 10 items of 390 documents
Cerebellar granule-cell-specific GABAAreceptors attenuate benzodiazepine-induced ataxia: evidence from α6-subunit-deficient mice
1999
Benzodiazepine- and alcohol-induced ataxias in rodents have been proposed to be affected by the gamma-aminobutyric acid type A (GABAA) receptor alpha 6 subunit, which contributes to receptors specifically expressed in cerebellar granule cells. We have studied an alpha 6 -/- mouse line for motor performance and drug sensitivity. These mice, as a result of a specific genetic lesion, carry a precise impairment at their Golgi-granule cell synapses. On motor performance tests (rotarod, horizontal wire, pole descending, staircase and swimming tests) there were no robust baseline differences in motor function or motor learning between alpha 6 -/- and alpha 6 +/+ mice. On the rotarod test, however,…
Hardwiring the Brain: Endocannabinoids Shape Neuronal Connectivity
2007
The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB 1 cannabinoid receptors (CB 1 Rs) are enriched in the axonal growth cones of γ-aminobutyric acid–containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB 1 R internalization and elimination from filopodia and induce chemorepulsion and collapse of axonal growth cones of these GABAergic interneurons by activating RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis spinal neurons. These findings, together with the impaired target selection of cortical GABAergic interneurons lacking CB 1 Rs, identify endoc…
The Dual Role of the GABAA Receptor in Peripheral Inflammation and Neuroinflammation: A Study in Hyperammonemic Rats
2021
Cognitive and motor impairment in minimal hepatic encephalopathy (MHE) are mediated by neuroinflammation, which is induced by hyperammonemia and peripheral inflammation. GABAergic neurotransmission in the cerebellum is altered in rats with chronic hyperammonemia. The mechanisms by which hyperammonemia induces neuroinflammation remain unknown. We hypothesized that GABAA receptors can modulate cerebellar neuroinflammation. The GABAA antagonist bicuculline was administrated daily (i.p.) for four weeks in control and hyperammonemic rats. Its effects on peripheral inflammation and on neuroinflammation as well as glutamate and GABA neurotransmission in the cerebellum were assessed. In hyperammone…
Current Pharmacological Treatment of Painful Diabetic Neuropathy: A Narrative Review.
2020
Background and Objectives: Distal symmetrical polyneuropathy (DSPN) is one of the most common chronic complications of diabetes mellitus. Although it is usually characterized by progressive sensory loss, some patients may develop chronic pain. Assessment of DSPN is not difficult, but the biggest challenge is making the correct diagnosis and choosing the right treatment. The treatment of DSPN has three primary objectives: glycemic control, pathogenic mechanisms, and pain management. The aim of this brief narrative review is to summarize the current pharmacological treatment of painful DSPN. It also summarizes knowledge on pathogenesis-oriented therapy, which is generally overlooked in many p…
Effects of ovariectomy and steroid replacement on GABAA receptor binding in female rat brain.
1991
Abstract The specific binding of tritiated muscimol to γ-aminobutyric acid (GABA) receptor sites was studied in distinct brain areas of female rats during different endocrine states. In diestrous rats with intact ovaries the highest receptor densities were found in the cortex (10.24 pmol/mg protein) and the lowest concentrations in the mediobasal hypothalamus (3.29 pmol/mg protein). Four weeks after removal of the ovaries, the number of binding sites was enhanced up to 2.4-fold in all brain areas investigated: the preoptic brain area, mediobasal hypothalamus, corticomedial amygdala, and cerebral cortex. The affinity of the binding sites remained unchanged. Substitution of estradiol and prog…
Pharmacologic management of neuropathic pain: Evidence-based recommendations
2007
Patients with neuropathic pain (NP) are challenging to manage and evidence-based clinical recommendations for pharmacologic management are needed. Systematic literature reviews, randomized clinical trials, and existing guidelines were evaluated at a consensus meeting. Medications were considered for recommendation if their efficacy was supported by at least one methodologically-sound, randomized clinical trial (RCT) demonstrating superiority to placebo or a relevant comparison treatment. Recommendations were based on the amount and consistency of evidence, degree of efficacy, safety, and clinical experience of the authors. Available RCTs typically evaluated chronic NP of moderate to severe …
A retrospective study of 72 cases diagnosed with idiopathic trigeminal neuralgia in indian populace
2014
Context: Trigeminal neuralgia is as a chronic, debilitating condition, which can have a major impact on quality of life. There are few reports of trigeminal neuralgia in oriental populations. Objectives: To evaluate the retrospective data of the patients diagnosed with idiopathic trigeminal neuralgia and to understanding the disorder in the Indian populace. Methods: The retrospective data of 72 patients with typical idiopathic trigeminal neuralgia regarding age of onset, gender, site of involvement, clinical presentations and treatment received during three years of the follow up was collected and analyzed. Results: In the present retrospective study, the mean age was 54.9 years; female to …
Neurological impairment in experimental antiphospholipid syndrome is associated with increased ligand binding to hippocampal and cortical serotonergi…
2013
The antiphospholipid syndrome (APS) is an autoimmune disease where the presence of high titers of circulating autoantibodies causes thrombosis with consecutive infarcts. In experimental APS (eAPS), a mouse model of APS, behavioral abnormalities develop in the absence of vessel occlusion or infarcts. Using brain hemispheres of control and eAPS mice with documented neurological and cognitive deficits, we checked for lymphocytic infiltration, activation of glia and macrophages, as well as alterations of ligand binding densities of various neurotransmitter receptors to unravel the molecular basis of this abnormal behavior. Lymphocytic infiltrates were immunohistochemically characterized using a…
Cl−uptake promoting depolarizing GABA actions in immature rat neocortical neurones is mediated by NKCC1
2004
GABA is the principal inhibitory neurotransmitter in the mature brain, but during early postnatal development the elevated [Cl−]i in immature neocortical neurones causes GABAA receptor activation to be depolarizing. The molecular mechanisms underlying this intracellular Cl− accumulation remain controversial. Therefore, the GABA reversal potential (EGABA) or [Cl−]i in early postnatal rat neocortical neurones was measured by the gramicidin-perforated patch-clamp method, and the relative expression levels of the cation−Cl− cotransporter mRNAs (in the same cells) were examined by semiquantitative single-cell multiplex RT-PCR to look for statistical correlations with [Cl−]i. The mRNA expression …
Induction of neurosteroid synthesis by NMDA receptors in isolated rat retina: a potential early event in excitotoxicity
1998
Here we investigated the possible regulation of neurosteroidogenesis by N-methyl-D-aspartic acid (NMDA) receptor activation and addressed the hypothesis that neurosteroid synthesis may be involved in acute excitotoxicity. In the isolated retina, exposure to NMDA modified pregnenolone and pregnenolone sulphate formation. This effect was dose and time dependent, the synthesis being increased by relatively moderate NMDA doses (1-100 microM) within 30 min exposure and reduced to its control value by 60 min or by raising drug concentrations. NMDA-stimulated neurosteroid synthesis was blocked by (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate (MK-801) and 3(2-ca…