Montori, Sheyla, Dos Anjos, Severiano, Poole, Amy, Regueiro-Purrinos, Marta M, Llorente, Irene L, Darlison, Mark G, Fernandez-Lopez, Arsenio and Martinez-Villayandre, Beatriz (2012) Differential effect of transient global ischaemia on the levels of GABA(A) receptor subunit mRNAs in young and older rats. Neuropathology and Applied Neurobiology, 38 (7). pp. 710-722. ISSN 0305-1846

Abstract/Description

Aims: This study has investigated how global brain ischaemia/reperfusion (I/R) modifies levels of mRNAs encoding GABA(A) receptor alpha1, beta2 and gamma2 subunits and glutamic acid decarboxylase 65 (GAD65) in an age- and structure-dependent manner. Gene expression in response to treatment with the anti-inflammatory agent meloxicam was also investigated. Methods: Global ischaemia was induced in 3- and 18-month-old male Sprague-Dawley rats. CA1, CA3, and dentate gyrus (DG) hippocampal areas, cerebral cortex (CC) and caudate putamen (C-Pu) from sham-operated and I/R-injured animals were excised 48 h after the insult and prepared for quantitative polymerase chain reaction (qPCR) assays. Following I/R, meloxicam treatment was also carried out on young animals. Results: Data revealed significant decreases in the levels of all GABA(A) receptor subunit transcripts in the hippocampus of both young and older injured animals compared to sham-operated ones. In contrast, there was either an increase or no change in GAD65 mRNA levels. GABA(A) receptor subunit transcript decreases were also observed in the CC and C-Pu in young injured animals but not in the CC of the older injured ones; interestingly, significant increases were observed in the C-Pu of older injured animals compared to controls. Meloxicam treatment following the insult resulted in a diminution of the previously-described I/R response. Conclusions: The data indicate that I/R results in the modification of the levels of several gene transcripts involved in GABAergic signalling in both the pre- and postsynaptic components, of this neurotransmitter system, in an age- and structure-dependent manner.

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