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Gamma-aminobutyric Acid (gamma-aminobutyric + acid)
Terms modified by Gamma-aminobutyric Acid Selected AbstractsDark-rearing-induced reduction of GABA and GAD and prevention of the effect by BDNF in the mouse retinaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2006Eun-Jin Lee Abstract Gamma-aminobutyric acid (GABA) is an important retinal neurotransmitter. We studied the expression of GABA, glutamate decarboxylase 65 (GAD65) and GAD67 by immunocytochemistry and Western blot, in the retinas of control and dark-reared C57BL/6J black mice. This study asked three questions. First, is visual input necessary for the normal expression of GABA, GAD65 and GAD67? Second, can the retina recover from the effects of dark-rearing if returned to a normal light,dark cycle? Third, does BDNF prevent the influence of dark-rearing on the expression of GABA and GAD? At postnatal day 10 (P10), before eye opening, GABA immunoreactivity was present in the ganglion cell layer (GCL), in the innermost rows of the inner nuclear layer (INL) and throughout the inner plexiform layer (IPL) of control and dark-reared retinas. In P30 control retinas, GABA immunoreactivity showed similar patterns to those at P10. However, in P30 dark-reared retinas, the density of GABA-immunoreactive cells was lower in both the INL and GCL than in control retinas. In addition, visual deprivation retarded GABA immunoreactivity in the IPL. Western blot analysis showed corresponding differences in the levels of GAD65 but not of GAD67 expression between control and dark-rearing conditions. In our study, dark-rearing effects were reversed when the mice were put in normal cyclic light,dark conditions for 2 weeks. Moreover, dark-reared retinas treated with BDNF showed normal expression of both GABA and GAD65. Our data indicate that normal expression of GABA and GAD65 is dependent on visual input. Furthermore, the data suggest that BDNF controls this dependence. [source] Gastrointestinal motility and the brain-gut axisDIGESTIVE ENDOSCOPY, Issue 2 2003TADASHI ISHIGUCHI The role of the brain-gut axis in gastrointestinal motility is discussed according to the specific organs of the gastrointestinal tract. Not only clinical studies but basic animal research are reviewed. Although the mechanism of functional gut disorders remains to be clarified, recent data suggest that there is evidence that the brain-gut axis has significant effects on gastrointestinal motility. The major role of endoscopy in the diagnosis of functional gastrointestinal disorders is to exclude organic gastrointestinal disorders. In the esophagus, the lower esophageal sphincter and a gamma-aminobutyric acid B mechanism are considered to play important roles in gastroesophageal reflux disease. In the stomach, corticotropin-releasing factor, neuropeptide Y and other substances might be involved in the pathogenesis of non-ulcer dyspepsia. In the small intestine, corticotropin-releasing factor, gamma-aminobutyric acid B and other substances are considered to modulate intestinal transit via central mechanisms. In the colon, it is known that psychiatric factors are related to the onset and clinical course of irritable bowel syndrome. Serotonin, corticotropin-releasing factor, gamma-aminobutyric acid, orphanin FQ and neuropeptide Y have been reported as putative neurotransmitters. More efforts in basic science studies and animal and human studies of physiology of the gastointestinal tract are still required. These efforts will elucidate further mechanisms to clarify the etiology of motility disorders and encourage the investigation of new therapies in this field. [source] Amygdala amino acid and monoamine levels in genetically Fast and Slow kindling rat strains during massed amygdala kindling: a microdialysis studyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2004Rick S. Shin Abstract We investigated the neurochemistry of epileptic seizures in rats selectively bred to be seizure-prone (Fast) vs. seizure-resistant (Slow) to amygdala kindling. Microdialysis was used to measure levels of amino acids [glutamate, aspartate and gamma-aminobutyric acid (GABA)] and monoamines (noradrenaline, dopamine and serotonin) during ,massed' stimulation (MS) (every 6 min) of the ipsilateral amygdala for a total of 40 stimulation trials. Behavioral seizure profiles together with their afterdischarge thresholds (ADTs) and associated durations were assessed during the procedure, and subsequently were redetermined 1, 7 and 14 days later. Then normal ,daily' kindling commenced and continued until the animal reached the fully kindled state. During MS, several generalized seizures were triggered in Fast rats that were associated with long afterdischarge (AD) durations and intermittent periods of elevated thresholds, but in Slow rats, most stimulations were associated with stable ADTs and short ADs. Progressively increasing extracellular glutamate and decreasing GABA was observed in Fast rats during the MS, whereas Slow rats showed levels similar to baseline values. Levels of noradrenaline and dopamine, but not of serotonin, were also increased in both strains throughout the MS treatment. In Fast rats, a dramatic lengthening of AD durations occurred 7 and 14 days following MS, as well as subsequent strong positive transfer to daily kindling, all of which were not seen in Slow rats. Together, these results show that repeated, closely spaced stimulations of the amygdala can differentially alter excitatory and/or inhibitory transmitter levels in a seizure network, and that sensitivity to this manipulation is genetically determined. [source] An immunogold investigation of the distribution of GABA and glycine in nerve terminals on the somata of spherical bushy cells in the anteroventral cochlear nucleus of guinea pigEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2004S. Mahendrasingam Abstract Spherical bushy neurons in the anteroventral cochlear nucleus receive glutamatergic primary terminals from the cochlear nerve and terminals of noncochlear (i.e. nonprimary) origin, many of which colocalize gamma-aminobutyric acid (GABA) and glycine. Here the relationship between GABA and glycine in these terminals has been investigated using postembedding immunogold labelling. A significant negative correlation was found between the density of terminal labelling for GABA and for glycine in four guinea pigs. Terminals could be divided into three categories, GABA-only, glycine-only, or colocalizing depending on whether they had a significantly higher labelling density for either amino acid than the primary terminals. The overall labelling density in all four animals was significantly greater for GABA in GABA-only terminals than colocalizing ones but similar for glycine in both. Within the terminals, the labelling density over synaptic vesicles, nonvesicular regions of cytoplasm and mitochondria was also investigated. No significant difference was detected in the labelling density of vesicles compared with nonvesicular regions for either amino acid. However, a significant difference was found between the overall labelling density over mitochondria and nonvesicular regions for both. There was also significantly more mitochondrial GABA labelling in GABA-only terminals compared to colocalizing terminals but mitochondrial glycine labelling was similar in glycine-only and colocalizing terminals. Thus the level of GABA is higher in single than in colocalizing terminals, particularly in the mitochondria, but similar for glycine in both. It is possible therefore that the presence of glycine affects the level of GABA in the nonprimary terminals but that the presence of GABA does not affect the level of glycine. [source] Differential effects of acute and chronic exercise on plasticity-related genes in the rat hippocampus revealed by microarrayEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2002Raffaella Molteni Abstract Studies were performed to determine the effects of acute and chronic voluntary periods of exercise on the expression of hippocampal genes. RNAs from rodents exposed to a running wheel for 3, 7 and 28 days were examined using a microarray with 1176 cDNAs expressed primarily in the brain. The expression of selected genes was quantified by Taqman RT-PCR or RNase protection assay. The largest up-regulation was observed in genes involved with synaptic trafficking (synapsin I, synaptotagmin and syntaxin); signal transduction pathways (Ca2+/calmodulin-dependent protein kinase II, CaM-KII; mitogen-activated/extracellular signal-regulated protein kinase, MAP-K/ERK I and II; protein kinase C, PKC-,) or transcription regulators (cyclic AMP response element binding protein, CREB). Genes associated with the glutamatergic system were up-regulated (N -methyl- d -aspartate receptor, NMDAR-2A and NMDAR-2B and excitatory amino acid carrier 1, EAAC1), while genes related to the gamma-aminobutyric acid (GABA) system were down-regulated (GABAA receptor, glutamate decarboxylase GAD65). Brain-derived neurotrophic factor (BDNF) was the only trophic factor whose gene was consistently up-regulated at all timepoints. These results, together with the fact that most of the genes up-regulated have a recognized interaction with BDNF, suggest a central role for BDNF on the effects of exercise on brain plasticity. The temporal profile of gene expression seems to delineate a mechanism by which specific molecular pathways are activated after exercise performance. For example, the CaM-K signal system seems to be active during acute and chronic periods of exercise, while the MAP-K/ERK system seems more important during long-term exercise. [source] Possible Contribution of Central Gamma-Aminobutyric Acid Receptors to Resting Vascular Tone in Freely Moving RatsEXPERIMENTAL PHYSIOLOGY, Issue 5 2000Yumi Takemoto Previous studies have shown that central administration of GABA (gamma-aminobutyric acid), an inhibitory neurotransmitter, preferentially reduces hindquarters and carotid vascular resistances but not renal and coeliac vascular resistances in conscious rats. This study tested the hypothesis that these preferential actions of central GABA receptors are related to differences between vessels in resting autonomic vascular tone in freely moving rats. Rats were chronically implanted with intracisternal cannulas and/or electromagnetic probes to measure regional blood flows. In response to GABA administration, the changes in vascular resistance (arterial blood pressure/regional blood flow) of the hindquarters (n = 23) and carotid (n = 12) vascular beds were significantly and negatively correlated with basal vascular resistance. No such relationship was found for the renal (n = 21), coeliac (n = 13) and superior mesenteric (n = 23) vascular beds. This finding indicates that the responsiveness to GABA of brainstem pathways controlling the hindquarters and carotid vascular beds co-varies with resting resistance in hindquarters and carotid vessels. A similar analysis was performed, correlating the ongoing vascular resistance of each vessel with its response to ganglionic blockade by chlorisondamine. In this case, a significant negative correlation was also found for the hindquarters (n = 26) and carotid (n = 15) vascular beds, but not for the coeliac (n = 17) or superior mesenteric (n = 19) vessels. Together, these findings suggest that central GABA receptors accessible from the cisterna magna preferentially affect two vascular beds which, in the freely moving rat, show resting autonomic vascular tone. [source] Neurochemistry of Trigeminal Activation in an Animal Model of MigraineHEADACHE, Issue 2006Michael L. Oshinsky PhD Research techniques such as electrophysiology, cFos protein expression, and other measurements of neuronal activation provide insights into the pathophysiology of pain processing in migraine, but they do not indicate the specific neurotransmitter systems involved. This paper summarizes data from microdialysis experiments in which changes in the neurochemistry of the trigeminal nucleus caudalis (TNC) were monitored during dural stimulation. Microdialysis allows the measurement of extracellular concentrations of neurotransmitters in a small area of the brain, in vivo, by means of a probe equipped with a semipermeable membrane. Microdialysis enables direct measurement of changes in extracellular concentrations of neurotransmitters in the intact animal over time in response to dural inflammation. Following the activation of the dural nociceptors, changes in the extracellular amino acid neurotransmitters in the deep lamina of the TNC were tracked. A 5-minute application of inflammatory soup when compared with saline to the dura of rats induced a transient decrease in extracellular glutamate in the TNC at approximately 30 minutes postapplication. This short-lived decrease was followed by a continuous increase in extracellular glutamate to a level of approximately 3 times the baseline value at 3 hours after application of the inflammatory soup. The time course of this increase in extracellular glutamate correlated with changes in sensory thresholds on the face of the rat from electrophysiological recordings of secondary sensory neurons in the TNC. No significant differences between the inflammatory soup and saline conditions were observed for extracellular concentrations of aspartate (an excitatory amino acid) or the inhibitory neurotransmitters gamma-aminobutyric acid or glutamine. Results of these experiments support an integral role for glutamate in central sensitization of neurons in the TNC, and suggest an important contribution of glutamate to allodynia and hyperalgia in this animal model of migraine. [source] Antiepileptic Drugs: How They Work in HeadacheHEADACHE, Issue 2001F. Michael Cutrer MD Antiepileptic drugs (AEDs) are promising agents for the prevention of migraine and other head pain. Migraine and epilepsy share several clinical features and respond to many of the same pharmacologic agents, suggesting that similar mechanisms may be involved in their pathophysiology. The mechanisms of action of AEDs are not fully understood, and a single drug may have more than one mechanism, both in epilepsy and in migraine. Valproate, topiramate, and gabapentin are likely to affect nociception by modulating gamma-aminobutyric acid- (GABA-) and/or glutamate-mediated neurotransmission. All three AEDs enhance GABA-mediated inhibition. Valproate and gabapentin interfere with GABA metabolism to prevent its ultimate conversion to succinate, and topiramate potentiates GABA-mediated inhibition by facilitating the action of GABA receptors. In addition, topiramate acts directly on non- N -methyl-D-aspartate, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate glutamate receptors. Valproate, topiramate, and possibly gabapentin inhibit sodium ion channels. All three drugs modulate calcium ion channel activity. Valproate blocks T-type calcium ion channels; topiramate inhibits high-voltage-activated L-type calcium ion channels; and gabapentin binds to the ,2, subunit of L-type calcium ion channels. AEDs may be useful in migraine prevention through such mechanisms as modulating the biochemical phenomena of aura or acting directly on the nociceptive system. Further evaluations of AEDs in migraine models will provide a better understanding of the pathophysiology and prevention of migraine. [source] Glutamate spillover augments GABA synthesis and release from axodendritic synapses in rat hippocampusHIPPOCAMPUS, Issue 1 2010Misty M. Stafford Abstract Tight coupling between gamma-aminobutyric acid (GABA) synthesis and vesicle filling suggests that the presynaptic supply of precursor glutamate could dynamically regulate inhibitory synapses. Although the neuronal glutamate transporter excitatory amino acid transporter 3 (EAAT3) has been proposed to mediate such a metabolic role, highly efficient astrocytic uptake of synaptically released glutamate normally maintains low-extracellular glutamate levels. We examined whether axodendritic inhibitory synapses in stratum radiatum of hippocampal area CA1, which are closely positioned among excitatory glutamatergic synapses, are regulated by synaptic glutamate release via presynaptic uptake. Under conditions of spatially and temporally coordinated release of glutamate and GABA within pyramidal cell dendrites, blocking glial glutamate uptake enhanced quantal release of GABA in a transporter-dependent manner. These physiological findings correlated with immunohistochemical studies revealing expression of EAAT3 by interneurons and uptake of D-asparate into putative axodendritic inhibitory terminals only when glial uptake was blocked. These results indicate that spillover of glutamate between adjacent excitatory and inhibitory synapses can occur under conditions when glial uptake incompletely clears synaptically released glutamate. Our anatomical studies also suggest that perisomatic inhibitory synapses, unlike synapses within dendritic layers of hippocampus, are not capable of glutamate uptake and therefore transporter-mediated dynamic regulation of inhibition is a unique feature of axodendritic synapses that may play a role in maintaining a homeostatic balance of inhibition and excitation. © 2009 Wiley-Liss, Inc. [source] Germination Conditions Affect Physicochemical Properties of Germinated Brown Rice FlourJOURNAL OF FOOD SCIENCE, Issue 9 2009Phantipha Charoenthaikij ABSTRACT:, Germinated brown rice has been reported to be nutritious due to increased free gamma-aminobutyric acid (GABA). The physicochemical properties of brown rice (BR) and glutinous brown rice (GNBR) after germination as affected by different steeping times (24, 36, 48, and 72 h depending on the rice variety) and pHs of steeping water (3, 5, 7, and as-is) were determined and compared to those of the nongerminated one (control). As the steeping time increased or pH of steeping water decreased, germinated brown rice flours (GBRF) from both BR and GNBR had greater reducing sugar, free GABA and ,-amylase activity; while the total starch and viscosity were lower than their respective controls. GBRFs from both BR and GNBR prepared after 24-h steeping time at pH 3 contained a high content of free GABA at 32.70 and 30.69 mg/100 g flour, respectively. The peak viscosity of GBRF obtained from both BR and GNBR (7.42 to 228.22 and 4.42 to 58.67 RVU, respectively) was significantly lower than that of their controls (255.46 and 190.17 RVU, respectively). The principal component analysis indicated that the important variables for discriminating among GBRFs, explained by the first 2 components at 89.82% of total explained variance, were the pasting profiles, ,-amylase activity, and free GABA. [source] Pharmacological profile of an essential oil derived from Melissa officinalis with anti-agitation properties: focus on ligand-gated channelsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2008Sawsan Abuhamdah A dual radioligand binding and electrophysiological study, focusing on a range of ligand-gated ion channels, was performed with a chemically-validated essential oil derived from Melissa officinalis (MO), which has shown clinical benefit in treating agitation. MO inhibited binding of [35S] t -butylbicyclophosphorothionate (TBPS) to the rat forebrain gamma-aminobutyric acid (GABA)A receptor channel (apparent IC50 0.040±0.001 mg mL,1), but had no effect on N -methyl- d -aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropianate (AMPA) or nicotinic acetylcholine receptors. Electrophysiological analyses with primary cultures of rat cortical neurons demonstrated that MO reversibly inhibited GABA-induced currents in a concentration-dependent manner (0.01,1 mg mL,1), whereas no inhibition of NMDA- or AMPA-induced currents was noted. Interestingly, MO elicited a significant dose-dependent reduction in both inhibitory and excitatory transmission, with a net depressant effect on neurotransmission (in contrast to the classical GABAA antagonist picrotoxinin which evoked profound epileptiform burst firing in these cells). The anti-agitation effects in patients and the depressant effects of MO in in-vitro we report in neural membranes are unlikely to reflect a sedative interaction with any of the ionotropic receptors examined here. [source] Altered Motor Cortex Excitability to Magnetic Stimulation in Alcohol Withdrawal SyndromeALCOHOLISM, Issue 4 2010Raffaele Nardone Background:, Alcohol addiction is a complex brain disease caused by alterations in crucial neurotransmitter systems, including gamma-aminobutyric acid (GABA) and glutamate. These disturbances could be revealed by changes in cortical excitability parameters, as assessed by transcranial magnetic stimulation (TMS). This study was aimed to further investigate the complex pathophysiology of alcohol withdrawal syndrome (AWS). Methods:, Motor cortex excitability was examined in 13 subjects with AWS in a mild predelirial state, in 12 chronic alcoholics and in 15 age-matched control subjects, using a range of TMS protocols. Central motor conduction time, resting and active motor threshold, duration of the cortical silent period, short latency intracortical inhibition (SICI), and intracortical facilitation (ICF) to paired TMS were examined. Results:, Intracortical facilitation was significantly increased in the AWS patients when compared with the chronic alcoholics and the control subjects. The other TMS parameters did not differ significantly from the controls. Administration of a single oral dose of the glutamatergic antagonist riluzole in a subgroup of 8 patients significantly reduced ICF; motor threshold and SICI were not affected by riluzole. Conclusion:, Transcranial magnetic stimulation shows a selective increase in intracortical facilitation after ethanol withdrawal. Our findings support the theory that altered glutamatergic receptor function plays an important role in the pathogenesis of human alcohol withdrawal. This study provides further physiological evidence that antiglutamatergic approaches represent an efficacious alternative for treating alcohol withdrawal symptoms. [source] GABAmimetic intravenous anaesthetics inhibit spontaneous Ca2+ -oscillations in cultured hippocampal neuronsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2006B. Sinner Background:, Spontaneous Ca2+ -oscillations are a possible mechanism of Ca2+ -mediated signal transduction in neurons. They develop by a periodical interplay of Ca2+, which enters the neuron from the extracellular medium and triggers Ca2+ release from the endoplasmic reticulum (ER). Ca2+ -oscillations are terminated by reuptake into the ER or plasmalemmal extrusion. Spontaneous Ca2+ -oscillations are glutamate dependent and appear to be responsible for neuronal plasticity and integration of information. Here, we examined the role of the gamma-aminobutyric acid (GABAA) receptor on spontaneous Ca2+ -oscillations and studied the effects of the anaesthetics midazolam, thiopental and the non-anesthetic barbituric acid on spontaneous Ca2+ -oscillations. Methods:, Hippocampal neuronal cell cultures of 19-day-old embryonic Wistar rats 17,18 days in culture were loaded with the Ca2+ -sensitive dye Fura-2AM. Experiments were performed using dual wave-length excitation fluorescence microscopy and calibration constants were obtained from in situ calibration. Results:, Spontaneous Ca2+ -oscillations are influenced by the GABAA receptor. The intravenous anaesthetics midazolam and thiopental suppressed the amplitude and frequency reversibly in a dose-dependent manner with EC50 in clinically relevant concentrations. This effect was mediated via the GABAA receptor as it could be reversed by the GABAA receptor antagonist bicuculline. In contrast, the application of barbituric acid had no effects on the spontaneous Ca2+ -oscillations. Conclusion:, Spontaneous Ca2+ -oscillations are influenced by the GABAA receptor. Spontaneous Ca2+ -oscillations might represent an interesting model system to study anaesthetic mechanisms on neuronal information processing. [source] Transcriptional profiling of hexaploid wheat (Triticum aestivum L.) roots identifies novel, dehydration-responsive genesPLANT CELL & ENVIRONMENT, Issue 5 2007MOHSEN MOHAMMADI ABSTRACT We used a long-oligonucleotide microarray to identify transcripts that increased or decreased in abundance in roots of dehydration-tolerant hexaploid bread wheat, in response to withholding of water. We observed that the major classes of dehydration-responsive genes (e.g. osmoprotectants, compatible solutes, proteases, glycosyltransferases/hydrolases, signal transducers components, ion transporters) were generally similar to those observed previously in other species and osmotic stresses. More specifically, we highlighted increases in transcript expression for specific genes including those putatively related to the synthesis of asparagine, trehalose, oligopeptide transporters, metal-binding proteins, the gamma-aminobutyric acid (GABA) shunt and transcription factors. Conversely, we noted a decrease in transcript abundance for diverse classes of glutathione and sulphur-related enzymes, specific amino acids, as well as MATE-efflux carrier proteins. From these data, we identified a novel, dehydration-induced putative AP2/ERF transcription factor, which we predict to function as a transcriptional repressor. We also identified a dehydration-induced ,little protein' (LitP; predicted mass: 8 kDa) that is highly conserved across spermatophytes. Using qRT-PCR, we compared the expression patterns of selected genes between two related wheat genotypes that differed in their susceptibility to dehydration, and confirmed that these novel genes were highly inducible by water limitation in both genotypes, although the magnitude of induction differed. [source] Inhibitory actions of the gamma-aminobutyric acid in pediatric Sturge-Weber syndrome,ANNALS OF NEUROLOGY, Issue 2 2009Roman Tyzio PhD Objective The mechanisms of epileptogenesis in Sturge-Weber syndrome (SWS) are unknown. We explored the properties of neurons from human pediatric SWS cortex in vitro and tested in particular whether gamma-aminobutyric acid (GABA) excites neurons in SWS cortex, as has been suggested for various types of epilepsies. Methods Patch-clamp and field potential recordings and dynamic biphoton imaging were used to analyze cortical tissue samples obtained from four 6- to 14-month-old pediatric SWS patients during surgery. Results Neurons in SWS cortex were characterized by a relatively depolarized resting membrane potential, as was estimated from cell-attached recordings of N-methyl-D-aspartate channels. Many cells spontaneously fired action potentials at a rate proportional to the level of neuronal depolarization. The reversal potential for GABA-activated currents, assessed by cell-attached single channel recordings, was close to the resting membrane potential. All spontaneously firing neurons recorded in cell-attached mode or imaged with biphoton microscopy were inhibited by GABA. Spontaneous epileptiform activity in the form of recurrent population bursts was suppressed by glutamate receptor antagonists, the GABA(A) receptor agonist isoguvacine, and the positive allosteric GABA(A) modulator diazepam. Blockade of GABA(A) receptors aggravated spontaneous epileptiform activity. The NKCC1 antagonist bumetanide had little effect on epileptiform activity. Interpretation SWS cortical neurons have a relatively depolarized resting membrane potential and spontaneously fire action potentials that may contribute to increased network excitability. In contrast to previous data depicting excitatory and proconvulsive actions of GABA in certain pediatric and adult epilepsies, GABA plays mainly an inhibitory and anticonvulsive role in SWS pediatric cortex. Ann Neurol 2009;66:209,218 [source] Advances in the pathophysiology of status epilepticusACTA NEUROLOGICA SCANDINAVICA, Issue 2007J. W. Y. Chen Status epilepticus (SE) describes an enduring epileptic state during which seizures are unremitting and tend to be self-perpetuating. We describe the clinical phases of generalized convulsive SE, impending SE, established SE, and subtle SE. We discuss the physiological and biochemical cascades which characterize self-sustaining SE (SSSE) in animal models. At the transition from single seizures to SSSE, GABAA (gamma-aminobutyric acid) receptors move from the synaptic membrane to the cytoplasm, where they are functionally inactive. This reduces the number of GABAA receptors available for binding GABA or GABAergic drugs, and may in part explain the development of time-dependent pharmacoresistance to benzodiazepines and the tendency of seizures to become self-sustaining. At the same time, ,spare' subunits of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartic acid) receptors move from subsynaptic sites to the synaptic membrane, causing further hyperexcitability and possibly explaining the preserved sensitivity to NMDA blockers late in the course of SE. Maladaptive changes in neuropeptide expression occur on a slower time course, with depletion of the inhibitory peptides dynorphin, galanin, somatostatin and neuropeptide Y, and with an increased expression of the proconvulsant tachykinins, substance P and neurokinin B. Finally, SE-induced neuronal injury and epileptogenesis are briefly discussed. [source] Effects of (-)bicuculline and gamma-aminobutyric acid on the NiCl2 mediated stimulation of the ERG b-wave amplitude from the isolated superfused vertebrate retinaACTA OPHTHALMOLOGICA, Issue 2007T SCHNEIDER Purpose: NiCl2 (15 ,M) stimulates the b-wave amplitude of vertebrate retina, up to 1.5-fold through its blocking of E/R-type voltage-gated Ca2+ channels. Assuming that these channels may trigger the release of the inhibitory neurotransmitter GABA, we tested the effect of (-)bicuculline and GABA itself. Methods: We have used a superfused vertebrate retina assay, testing retina from bovine (Lüke et al., 2005: Brain Res Brain Res Protoc 16 : 27-36). The retina was separated from the underlying pigment epithelium and mounted on a mesh occupying the center of the perfusing chamber. The electroretinogram was recorded in the surrounding nutrient medium via two silver/silver-chloride electrodes on either side of the retina. The recording chamber containing a piece of retina was placed in an electrically and optically insulated air thermostat. The retina was dark-adapted and the electroretinogram was elicited at intervals of five min using a single white flash for stimulation. Results: (-)Bicuculline increased the b-wave amplitude to a similar extent as observed in parallel recordings for low NiCl2 (15 ,M). The GABA effect was biphasic, and let to a transient stimulation after NiCl2 application. Those retina segments which did not respond to NiCl2 (15 ,M), also could not be stimulated by bicuculline and vice versa. Conclusions: The stimulatory effect of NiCl2 on the ERG b-wave amplitude is mediated by a NiCl2-sensitive, probably Cav2.3 / voltage-gated Ca2+-channel triggered GABA-release, and GABA itself may act on at least two different receptors. [source] | |||||||||||||