Distribution of alcohol dehydrogenase mRNA in the rat central nervous system - Consequences for brain ethanol and retinoid metabolism

The localization of alcohol dehydrogenase (ADH) in brain regions would demo nstrate active ethanol metabolism in brain during alcohol consumption, whic h would be a new basis to explain the effects of ethanol in the central ner vous system. Tissue sections from several regions of adult rat brain were e xamined by in situ hybridization to detect the expression of genes encoding ADH1 and ADH4, enzymes highly active with ethanol and retinol. ADH1 mRNA w as found in the granular and Purkinje cell layers of cerebellum, in the pyr amidal and granule cells of the hippocampal formation and in some cell type s of cerebral cortex. ADH4 expression was detected in the Purkinje cells, i n the pyramidal and granule cells of the hippocampal formation and in the p yramidal cells of cerebral cortex. High levels of ADH1 and ADH4 mRNAs were detected in the CNS epithelial and vascular tissues: leptomeninges, choroid plexus, ependymocytes of ventricle walls, and endothelium of brain vessels . Histochemical methods detected ADH activity in rodent cerebellar slices, while Western-blot analysis showed ADH4 protein in homogenates from several brain regions. In consequence, small but significant levels of ethanol met abolism can take place in distinct areas of the CNS following alcohol consu mption, which could be related to brain damage caused by a local accumulati on of acetaldehyde. Moreover, the involvement of ADH in the synthesis of re tinoic acid suggests a role for the enzyme in the regulation of adult brain functions. The impairment of retinol oxidation by competitive inhibition o f ADH in the presence of ethanol may be an additional origin of CNS abnorma lities caused by ethanol.