Effects of alcohol on brain-derived neurotrophic factor mRNA expression indiscrete regions of the rat hippocampus and hypothalamus

Chronic alcohol consumption has adverse effects on the central nervous syst em, affecting some hippocampal and hypothalamic functions. In this study we tempted to demonstrate that some of these modifications could involve impa irment of neurotrophic factors. Three experimental groups of male Sprague D awley rats were studied: one control group, one chronically treated with al cohol vapor according to a well-established model that induces behavioral d ependence, and a third group treated similarly but killed 12 hr after alcoh ol withdrawal. In all groups, changes in brain-derived neurotrophic factor mRNA expression occurring in the hippocampus and supraoptic nucleus were fi rst analyzed by reverse transcription-polymerase chain reaction and then by in situ hybridization. In parallel, we used ribonuclease protection assay to measure mRNA levels encoding trkB in the two central nervous system regi ons. We showed that chronic alcohol intoxication decreases brain-derived ne urotrophic factor mRNA expression in discrete regions of the rat hippocampu s (CA1 region and dentate gyrus) and in the supraoptic nucleus of the hypot halamus. We also showed a global up-regulation of trkB mRNA expression enco ding the high-affinity brain-derived neurotrophic factor receptor (TrkB), a fter applying the same treatment. Following 12 hr of alcohol withdrawal, a significant increase in BDNF mRNA expression was observed in the dentate gy rus and CA3 region of hippocampus and in the hypothalamic supraoptic nucleu s. These findings suggest that chronic alcohol intake may modify hippocampa l and hypothalamic neuronal functions through modifications in growth facto rs and its receptors. (C) 2001 Wiley-Liss, Inc.