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 factor-2 (FGF-2) mRNA in brain regions of tel- and mesencephalon of rats suggesting that neuroprotective effect of (-)nicotine may, at least in part, involve an activation of the neuronal 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. This 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 time point examined. Using Western blot analysis it was found 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 (+/-)-epibatidine effects on FGF-2 expression were antagonized by the non-competitive nAChR antagonist mecamylamine, indicating an involvement of nicotinic receptors. In the same brain areas examined, no changes were observed in the fibroblast growth factor receptor-1 (FGFR-1) mRNA levels, in brain-derived neurotrophic factor (BDNF) and in glial cell line-derived neurotrophic factor (GDNF) mRNA levels. In view of the neurotrophic function of FGF-2, these results, together with previous ones, could further help to understand the molecular mechanisms mediating the previously observed neuroprotective effects of (-)nicotine.
Belluardo
N
N
Institute of Human Physiology, University of Palermo, Palermo, Italy. belluard@mbox.unict.it
Mudò
G
G
Blum
M
M
Cheng
Q
Q
Caniglia
G
G
Dell'Albani
P
P
Fuxe
K
K
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D017403:In Situ Hybridization; D008464:Mecamylamine / Q000494:pharmacology; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000235:genetics; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D019086:Bridged Bicyclo Compounds, Heterocyclic; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D008464:Mecamylamine; C082748:epibatidine