Chronic exposure to ethanol alters neurotrophin content in the basal forebrain-cortex system in the mature rat: effects on autocrine-paracrine mechanisms.

Neurotrophins are broadly expressed in the mammalian forebrain: notably in cerebral cortex and the basal forebrain (e.g., the septal and basal nuclei). These factors promote neuronal survival and plasticity, and have been implicated as key players in learning and memory. Chronic exposure to ethanol causes learning and memory deficits. We tested the hypothesis that ethanol affects neurotrophin expression and predicted that these changes would be consistent with alterations in retrograde or autocrine/paracrine systems. Mature rats were fed a liquid diet containing ethanol daily for 8 or 24 weeks. Weight-matched controls were pair-fed an isocaloric, isonutritive diet. Proteins from five structures (parietal and entorhinal cortices, hippocampus, and the basal and septal nuclei) were studied. ELISAs were used to determine the concentration of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3). All three neurotrophins were detected in each structure examined. Ethanol treatment significantly (p < 0.05) affected neurotrophin expression in time- and space-dependent manners. NGF content was generally depressed by ethanol exposure, whereas NT-3 content increased. BDNF concentration was differentially affected by ethanol: it increased in the parietal cortex and the basal forebrain and decreased in the hippocampus. With the exception of NGF in the septohippocampal system, the ethanol-induced changes in connected structures were inconsistent with changes that would be predicted from a retrograde model. Thus, the present data (a) support the concept that neurotrophins act through a nonretrograde system (i.e., a local autocrine/paracrine system), and (b) that chronic exposure to ethanol disrupts these regulatory mechanisms.