Differential effect of transient global ischaemia on the levels of g-aminobutyric acid type A (GABA A ) receptor subunit mRNAs in young and older rats S. Montori*, S. Dos_Anjos*, A. Poole§, M. M. Regueiro-Purriños†, I. L. Llorente*, M. G. Darlison§, A. Fernández-López* and B. Martínez-Villayandre‡ *Área de Biología Celular, Instituto de Biomedicina, †Área de Medicina y Cirugía Animal, ‡Área de Bioquímica y Biología Molecular, Universidad de León, León, Spain, and §School of Life, Sport and Social Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh, UK S. Montori, S. Dos_Anjos, A. Poole, M. M. Regueiro-Purriños, I. L. Llorente, M. G. Darlison, A. Fernández-López and B. Martínez-Villayandre (2012) Neuropathology and Applied Neurobiology 38, 710–722 Differential effect of transient global ischaemia on the levels of g-aminobutyric acid type A (GABAA) receptor subunit mRNAs in young and older rats Aims: This study has investigated how global brain ischaemia/reperfusion (I/R) modifies levels of mRNAs encoding g-aminobutyric acid type A (GABAA) receptor a1, b2 and g2 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 assays. Following I/R, meloxicam treatment was also carried out on young animals. Results: Data revealed sig- nificant decreases in the levels of all GABA A receptor subunit transcripts in the hippocampus of both young and older injured animals compared with sham-operated ones. In contrast, there was either an increase or no change in GAD65 mRNA levels. GABAA 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 with 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 neuro- transmitter system, in an age- and structure-dependent manner. Keywords: age, cerebral ischaemia, GABA A receptor, GAD65, meloxicam Introduction Mammalian g-aminobutyric acid (GABA) type A (GABAA) receptors (GABAARs) are heteropentameric chloride- selective ion channels that are assembled into a variety of subtypes from 16 subunits: a1–a6, b1–b3, g1–g3, d, e, p and q, each of which is encoded by a separate gene [1]. The prevalent native GABAAR stoichiometry is 2a:2b:1g, with a1b2g2 being the major subtype in the mammalian central nervous system (CNS) [2,3]. Each subtype pos- sesses different biophysical and pharmacological proper- ties and displays a distinct regional [4] and temporal [5] expression profile. GABAA receptors are of clinical Correspondence: Beatriz Martínez-Villayandre, Área de Bioquímica y Biología Molecular, Instituto de Biomedicina, Universidad de León, 24071 León, Spain. Tel: +34 987 291488; Fax: +34 987 291917; E-mail: beatriz.martinez@unileon.es Author website: http://neurobio.unileon.es/ictus 710 © 2012 The Authors Neuropathology and Applied Neurobiology © 2012 British Neuropathological Society Neuropathology and Applied Neurobiology (2012), 38, 710–722 doi: 10.1111/j.1365-2990.2012.01254.x