Ischaemia differentially regulates GABA(B) receptor subunits in organotypic hippocampal slice cultures

HI Cimarosti, S Kantamneni, JM Henley

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27 Citations (Scopus)

Abstract

Reduced synaptic inhibition due to dysfunction of ionotropic GABA(A) receptors has been proposed as one factor in cerebral ischaemia-induced excitotoxic cell death. However, the participation of the inhibitory metabotropic GABA(B) receptors in these pathological processes has not been extensively investigated. We used oxygen-glucose deprivation (OGD) and NMDA-induced excitotoxicity as models to investigate whether ischaemia-like challenges alter the protein levels of GABA(B1) and GABA(B2) receptor subunits in rat organotypic hippocampal slice cultures. Twenty-four hours after the insult both OGD and NMDA produced a marked decrease in the total levels of GABA(B2) ( approximately 75%), while there was no significant change in the levels of GABA(B1) after OGD, but an increase after NMDA treatment ( approximately 100%). The GABA(B) receptor agonist baclofen (100 muM) was neuroprotective following OGD or NMDA treatment if added before or during the insult. GABA(B) receptors comprise heterodimers of GABA(B1) and GABA(B2) subunits and our results suggest that the separate subunits are independently regulated in response to extreme neuronal stress. However, because GABA(B2) is required for functional surface expression, down-regulation of this subunit removes an important inhibitory feedback mechanism under pathological conditions.
Translated title of the contributionIschaemia differentially regulates GABA(B) receptor subunits in organotypic hippocampal slice cultures
Original languageEnglish
Pages (from-to)1088 - 1096
Number of pages9
JournalNeuropharmacology
Volume56
DOIs
Publication statusPublished - May 2009

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