title: 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.
abstract: 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 GABAA receptor subunits (α1, β2 and γ2), and the GABAergic presynaptic marker, glutamic acid decarboxylase (GAD65), were studied. Mortality assays revealed that GABAA 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.
authors: Área de Biología Celular, Instituto de Biomedicina, Universidad de León, 24071 León, Spain.
authors: Irene L
authors: IL
authors: Llorente
authors: Diego
authors: D
authors: Perez-Rodriguez
authors: Beatriz
authors: B
authors: Martínez-Villayandre
authors: Severiano
authors: S
authors: Dos-Anjos
authors: Mark G
authors: MG
authors: Darlison
authors: Amy V
authors: AV
authors: Poole
authors: Arsenio
authors: A
authors: Fernández-López
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000818:Animals; D015687:Cell Hypoxia; D002470:Cell Survival; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D066298:In Vitro Techniques; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology*; D015424:Reperfusion; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D027322:Amino Acid Transport System X-AG; D018696:Neuroprotective Agents; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D005947:Glucose
keywords: Brain slices; Chloride channel; Ex vivo; GABAergic system; Glutamatergic system; Mortality; Oxygen and glucose deprivation