ACUTE INTERMITTENT NICOTINE TREATMENT PRODUCES REGIONAL INCREASES OF BASIC FIBROBLAST GROWTH-FACTOR MESSENGER-RNA AND PROTEIN IN THE TELENCEPHALON AND DIENCEPHALON OF THE RAT

Several findings show a neuroprotective effect of nicotine treatment i n different experimental models, and a negative correlation has been o bserved between cigarette smoking and the incidence of Parkinson's dis ease. It seems possible that nicotine may in part exert its neuroprote ctive actions by favouring the synthesis of neurotrophic factors. The aim of this study was to determine whether the nicotine treatment coul d be associated with the induction of a neurotrophic factor in brain r egions with nicotinic receptors. Thus, we analysed by in situ hybridiz ation and RNAse protection assay the effects of (-)nicotine on basic f ibroblast growth factor messenger RNA and by immunocytochemistry fibro blast growth factor-2 protein in the tel-and diencephalon of rats foll owing single or acute intermittent (-)nicotine treatment. The present results showed that acute intermittent (-)nicotine treatment (four i.p . injections at intervals of 30 min), but not single injections, lead to a substantial and dose-related (0.1-2 mg/kg) up-regulation of fibro blast growth factor-2 messenger RNA levels in the cerebral cortex, in the hippocampus, in the striatum and ventral midbrain. This induction of fibroblast growth factor-2 expression peaked 4 h after the first in jection and returned to normal levels within 24 h. The change of fibro blast growth factor-2 messenger RNA levels was associated with increas ed fibroblast growth factor-2 immunoreactivity mainly localized to ner ve cells. The treatment was effective also when repeated in the same a nimals three or five days after the first injection. The pre-treatment with the non-competitive (-)nicotine receptor antagonist mecamylamine blocked the (-)nicotine effects on fibroblast growth factor-2 messeng er RNA levels. In the above areas, no changes were observed in the fib roblast growth factor-1, 2 and 3 receptor messenger RNA levels nor in brain-derived neurotrophic Factor messenger RNA levels. The present da ta indicate an ability of intermittent(-)nicotine to increase fibrobla st growth factor-2 in many tel-and diencephalic areas. In view of the trophic function of fibroblast growth factor-2, the previously observe d neuroprotective effects of (-)nicotine may at least in part involve an activation of the neuronal fibroblast growth factor-2 signalling, a nd open up new avenues for treatment of Parkinson's disease and Alzhei mer's disease based on the existence of nicotinic receptor subtypes en hancing fibroblast growth factor-2 signalling in many regions of the t el-and diencephalon. (C) 1998 Published by Elsevier Science Ltd.