Striatal increase of neurotrophic factors as a mechanism of nicotine protection in experimental parkinsonism.
The repeated finding of an apparent protective effect of cigarette smoking on the risk of Parkinson's disease is one of the few consistent results in the epidemiology of this disorder. Among the innumerous substances that originate from tobacco smoke, nicotine is by far the most widely studied, and the most likely candidate for a protective effect against neuronal degeneration in Parkinson's disease. Nicotine is a natural alkaloid that has considerable stimulatory effects on the central nervous system (CNS). Its effects on the CNS are mediated by the activation of neuronal heteromeric acetylcholine-gated ion channel receptors (nAChR, also termed nicotinic acetylcholine receptors). In the present study, we describe the neuroprotective effects of (-)nicotine in two animal models of parkinsonism: the diethyldithiocarbamate (DDC)-induced enhancement of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity in mice, and the methamphetamine-induced neurotoxicity in rats and mice. In parallel experiments, we found that (-)nicotine induces the basic fibroblast growth factor (FGF-2) and the brain-derived neurotrophic factor (BDNF) in rat striatum. As FGF-2 and BDNF have been reported to be neuroprotective for dopaminergic cells, our data indicate that the increase in neurotrophic factors is a possible mechanism by which (-)nicotine protects from experimental parkinsonisms. Moreover, they suggest that nAChR agonists could be of potential benefit in the progression of Parkinson's disease.
Maggio
R
R
Institute of Pharmacology, University of Pisa, Italy.
Riva
M
M
Vaglini
F
F
Fornai
F
F
Racagni
G
G
Corsini
G U
GU
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002478:Cells, Cultured; D018765:Dopamine Uptake Inhibitors; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008694:Methamphetamine; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009498:Neurotoxins; D009538:Nicotine / Q000627:therapeutic use*; D010302:Parkinson Disease, Secondary / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D018765:Dopamine Uptake Inhibitors; D018696:Neuroprotective Agents; D009498:Neurotoxins; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D008694:Methamphetamine; D009538:Nicotine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase