GABA_A receptor chloride channels are involved in the neuroprotective role of GABA following oxygen and glucose deprivation in the rat cerebral cortex but not in the hippocampus

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• 作者：Irene L. Llorente ; Diego Perez-Rodriguez ; Beatriz Mart¨ªnez-Villay ; re ; Severiano Dos-Anjos ; Mark G. Darlison ; Amy V. Poole ; Arsenio Fern¨¢ndez-L¨®pez
• 关键词：Brain slices ; Chloride channel ; Ex vivo ; GABAergic system ; Glutamatergic system ; Mortality ; Oxygen and glucose deprivation
• 刊名：Brain Research
• 出版年：2013
• 出版时间：2 October, 2013
• 年：2013
• 卷：1533
• 期：Complete
• 页码：141-151
• 全文大小：6295 K

文摘

Assays on ¡°ex vivo¡± sections of rat hippocampus and rat cerebral cortex, subjected to oxygen and glucose deprivation (OGD) and a three-hour reperfusion-like (RL) recovery, were performed in the presence of either GABA or the GABA_A receptor binding site antagonist, bicuculline. Lactate dehydrogenase (LDH) and propidium iodide were used to quantify cell mortality. We also measured, using real-time quantitative polymerase chain reaction (qPCR), the early transcriptional response of a number of genes of the glutamatergic and GABAergic systems. Specifically, glial pre- and post-synaptic glutamatergic transporters (namely GLAST1a, EAAC-1, GLT-1 and VGLUT1), three GABA_A receptor subunits (¦Á1, ¦Â2 and ¦Ã2), and the GABAergic presynaptic marker, glutamic acid decarboxylase (GAD65), were studied. Mortality assays revealed that GABA_A receptor chloride channels play an important role in the neuroprotective effect of GABA in the cerebral cortex, but have a much smaller effect in the hippocampus. We also found that GABA reverses the OGD-dependent decrease in GABA_A receptor transcript levels, as well as mRNA levels of the membrane and vesicular glutamate transporter genes. Based on the markers used, we conclude that OGD results in differential responses in the GABAergic presynaptic and postsynaptic systems.