Edinburgh Napier University

  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.