title: Acute intermittent nicotine treatment induces fibroblast growth factor-2 in the subventricular zone of the adult rat brain and enhances neuronal precursor cell proliferation.
abstract: Over the past years, evidence has accumulated that stem cells are present in the adult brain, and generate neurons and/or glia from two active germinal zones: the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus. This study shows that acute intermittent nicotine treatment significantly enhances neuronal precursor cell proliferation in the SVZ of adult rat brain, but not in the SGZ of the hippocampus, and pre-treatment with mecamylamine, a nonselective nAChR antagonist, blocks the enhanced precursor proliferation by nicotine. This effect is supported by up-regulation of fibroblast growth factor-2 (FGF-2) mRNA in the SVZ and the expression of its receptor FGFR-1 in cells of SVZ showing precursor cells profile. It is also demonstrated that the nicotine effect on neuronal precursor proliferation is mediated by FGF-2 via fibroblast growth factor receptor 1 (FGFR-1) activation by showing that i.c.v. pre-treatment with anti-FGF-2 antibodies or with FGFR-1 inhibitor 3-[(3-(2-carboxyethyl)-4-methylpyrrol-2-yl)methylene]-2-indolinone (SU5402) blocks nicotine-induced precursor cell proliferation. This nicotine enhancement of neuronal precursor cell proliferation was not accompanied by an increase in the number of apoptotic cells. Taken together the present findings revealed the existence in the SVZ of the adult rat brain of a trophic mechanism mediated by FGF-2 and its receptor and regulated by nAchR activation. This possibility of in vivo regulation of neurogenesis in the adult brain by exogenous factors may aid to develop treatments stimulating neurogenesis with potential therapeutic implications.
authors.affiliation: University of Palermo, Department of Experimental Medicine, Division of Human Physiology, Corso Tukory 129, 90134 Palermo, Italy. g.mudo@unipa.it
authors.forename: G
authors.initials: G
authors.lastname: Mudò
authors.forename: N
authors.initials: N
authors.lastname: Belluardo
authors.forename: A
authors.initials: A
authors.lastname: Mauro
authors.forename: K
authors.initials: K
authors.lastname: Fuxe
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020547:Lateral Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology* / Q000627:therapeutic use; D018722:Nicotinic Agonists / Q000494:pharmacology / Q000627:therapeutic use; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011758:Pyrroles; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; C105686:SU 5402; D016222:Fibroblast Growth Factor 2; D009538:Nicotine; D051496:Receptor, Fibroblast Growth Factor, Type 1