DEGENERATION OF RAT CHOLINERGIC BASAL FOREBRAIN NEURONS AND REACTIVE CHANGES IN NERVE GROWTH-FACTOR EXPRESSION AFTER CHRONIC NEUROTOXIC INJURY .2. REACTIVE EXPRESSION OF THE NERVE GROWTH-FACTOR GENE IN ASTROCYTES

Long-term consumption of ethanol both in human and rodent induces a pr ocess of chronic degeneration of cholinergic basal forebrain neurons w hich results in a cholinergic deafferentation of the cortical mantle. We have used quantitative northern blot analysis and in situ hybridiza tion to demonstrate that these degenerative events in rat evoke an inc rease in the expression of the nerve growth factor gene in a number of brain areas, including the cholinergic basal forebrain nuclei and the ir cortical target regions. By combining non-radioactive in situ hybri dization and immunohistochemistry activated astrocytes were identified as the major source of altered nerve growth factor gene expression. T his increased nerve growth factor expression is paralleled by a dendri tic remodelling of basal forebrain neurons, while the expression of ch oline acetyltransferase in surviving neurons remains the same. This fa ilure of nerve growth factor to rescue the expression of choline acety ltransferase differs from the effects of exogenously administered nerv e growth factor in acutely lesioned systems. The results indicate that under certain conditions of chronic neurodegeneration, the utilizatio n of nerve growth factor might be impaired, which could be due to a de fective nerve growth factor signalling mechanism.