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 dysfunction associated with Alzheimer's disease (AD). In rats, NGF activates gene expression of the acetylcholine synthetic enzyme choline acetyltransferase (ChAT) and prevents age- and lesion-induced degeneration of basal forebrain (BF) cholinergic neurons. Cholinergic neurons in the BF coexpress galanin (GAL), a neuropeptide that has been shown to impair performance on memory tasks possibly through the inhibition of cholinergic memory pathways. NGF up-regulates both ChAT and GAL gene expression in cultured pheochromocytoma cells; however, the effect of chronic in vivo NGF administration on GAL gene expression within the BF has not been studied. We used in situ hybridization and quantitative autoradiography 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 ChAT gene expression, NGF strongly up-regulated the GAL gene in the rat cholinergic BF. NGF had no effect on GAL gene expression in other noncholinergic 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 up-regulates GAL gene expression in the cholinergic BF. These results suggest that the concurrent induction of GAL in the BF could limit the ameliorating actions of NGF on cholinergic dysfunction.
Planas
B
B
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle 98195, USA.
Kolb
P E
PE
Raskind
M A
MA
Miller
M A
MA
D000818:Animals; D002795:Choline O-Acetyltransferase / Q000235:genetics*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D019004:Galanin / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008297:Male; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D009496:Neurotensin / Q000235:genetics; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012688:Septum Pellucidum / Q000187:drug effects / Q000378:metabolism
D009414:Nerve Growth Factors; D009496:Neurotensin; D019004:Galanin; D002795:Choline O-Acetyltransferase