NERVE GROWTH-FACTOR INDUCES GALANIN GENE-EXPRESSION IN THE RAT BASAL FOREBRAIN - IMPLICATIONS FOR THE TREATMENT OF CHOLINERGIC DYSFUNCTION

Nerve growth factor (NGF) is a potential treatment for cholinergic dys function associated with Alzheimer's disease (AD). In rats, NGF activa tes gene expression of the acetylcholine synthetic enzyme choline acet yltransferase (ChAT) and prevents age- and lesion-induced degeneration of basal forebrain (BF) cholinergic neurons. Cholinergic neurons in t he BF coexpress galanin (GAL), a neuropeptide that has been shown to i mpair performance on memory tasks possibly through the inhibition of c holinergic memory pathways. NGF up-regulates both ChAT and GAL gene ex pression in cultured pheochromocytoma cells; however, the effect of ch ronic in vivo NGF administration on GAL gene expression within the BF has not been studied. We used in situ hybridization and quantitative a utoradiography to assess GAL and ChAT gene expression within the BF of adult male rats following chronic intracerebroventricular infusion of NGF or cytochrome c. We now report that, in addition to stimulating C hAT gene expression, NGF strongly up-regulated the GAL gene in the rat cholinergic BF. NGF had no effect on GAL gene expression in other non cholinergic forebrain regions. NGF induction of GAL gene expression in the BF was specific, because gene expression for another neuropeptide , neurotensin, present within noncholinergic BF neurons was unchanged. Our data provide the first evidence that in vivo NGF administration u p-regulates GAL gene expression in the cholinergic BF. These results s uggest that the concurrent induction of GAL in the BF could limit the ameliorating actions of NGF on cholinergic dysfunction. (C) 1997 Wiley -Liss, Inc.