Differential regulation of forebrain glutamic acid decarboxylase mRNA expression by aging and stress

In aging brain, degeneration or functional impairment of the hippocampus ha s been connected with stress dysregulation, serving to disinhibit stress re sponses and allow for glucocorticoid hypersecretion and its attendant patho physiology. Hippocampal dysfunction appears to be communicated to paraventr icular hypothalamic corticotropin-releasing hormone neurons by way of subco rtical GABAergic neurons. As such, hippocampal-hypothalamic relays are like ly to play an important role in age-related stress dysfunction. To test thi s hypothesis, regulation of glutamic acid decarboxylase, isoform mRNA was s tudied in young (3 months), middle aged (15 months) and aged (30 months) Fi scher 344/Brown Norway Fl hybrid rats. Basal expression of glutamic acid de carboxylase (GAD) 65 mRNA was increased in the medial preoptic area and pos teromedial bed nucleus of the stria terminalis (BST) in aged rats relative to both middle-aged and young groups. Unlike young or middle-aged animals, exposure to chronic intermittent stress decreased GAD65 mRNA levels in the medial preoptic area and posteromedial BST of aged rats. Thus, while aged r ats show evidence of elevated basal GABA synthesis, chronic stress causes d ifferential loss of GAD in hippocampal-PVN relays, consistent with reduced PVN inhibition. (C) 2001 Elsevier Science B.V. All rights reserved.