The nicotinic acetylcholine receptor agonist (+/-)-epibatidine increases FGF-2 mRNA and protein levels in the rat brain

In a previous work, we showed that acute intermittent nicotine treatment up -regulates the level of fibroblast growth faster-2 (FGF-2) mRNA in brain re gions of tel- and mesencephalon of rats suggesting that neuroprotective eff ect of (-)nicotine may, at least in parr, involve an activation of the neur onal FGF-2 signalling. The present experiments were designed to extend the study on the nicotinic receptor mediated up-regulation of FGF-2 mRNA levels to the use of the potent nicotinic acetylcholine receptor (nAChR) agonist (+/-)-epibatidine. The (+/-)-epibatidine treatment led to a strong and long lasting up-regulation of FGF-2 mRNA expression in the cerebral cortex, in the hippocampal formation, in the striatum and in the substantia nigra. Thi s FGF-2 mRNA induction, already statistically significant at 4 h, peaked at 12 h from treatment and was only partially returned towards normal levels at 48 h, the last rime point examined. Using Western blot analysis it was f ound that the epibatidine-induced upregulation of FGF-mRNA is accompaned by an increase of FGF-2 protein level at the 20-h time-interval. These (+/-)- epibaridine effects on FGF-2 expression were antagonized by the non-competi tive nAChR antagonist mecamylamine, indicating an involvement of nicotinic receptors. In the same brain areas examined, no changes were observed in th e fibroblast growth factor receptor-1 (FGFR-1) mRNA levels, in bt ain-deriv ed neurotrophic factor (BDNF) and in glial cell line-derived neurotrophic f actor (GDNF) mRNA levels. In view of the neurotrophic function of FGF-2, th ese results, together with previous ones, could further help to understand the molecular mechanisms mediating the previously observed neuroprotective effects of (-)nicotine. (C) 1999 Published by Elsevier science B.V. All rig hts reserved.