Stimulation of non-α7 nicotinic receptors partially protects dopaminergic neurons from 1-methyl-4-phenylpyridinium-induced toxicity in culture

被引:65
作者
Jeyarasasingam, G [1 ]
Tompkins, L [1 ]
Quik, M [1 ]
机构
[1] Parkinsons Inst, Sunnyvale, CA 94089 USA
关键词
mesencephalic cells; 1-methyl-4-phenylpyridinium; neuroprotection; tyrosine hydroxylase; nicotine; Parkinson's disease;
D O I
10.1016/S0306-4522(01)00488-2
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Previous work has shown that nicotine treatment protects against nigrostriatal degeneration in rodents, findings that may be of relevance to the decreased incidence of Parkinson's disease in cigarette smokers. In the present studies, we investigated the effect of nicotine against 1-methyl-4-phenylpyridinium-induced toxicity in dopaminergic ventral mesencephalic cultures to identify the nicotinic receptor population that may be involved. [H-3]Epibatidine, a ligand that binds to receptors containing alpha2-alpha6 subunits, bound to at least two populations of sites that were up-regulated by nicotine in a time and dose dependent manner. We next examined the effect of nicotine on cultures treated with 1-methyl-4-phenylpyridinium a neurotoxin that selectively damages nigrostriatal dopaminergic neurons. Pre-treatment with nicotine, at 10(-7)-10(-4) M, partially prevented the toxin-induced decline in dopaminergic cells. Pre-exposure to nicotine for 24 h resulted in optimal protection, suggesting that receptor tip-regulation may contribute to the observed neuroprotective effect. Nicotine-mediated protection was blocked by pre-incubation with the nicotinic receptor antagonist d-tubocurarine (10(-4) M), but not the alpha7 receptor-selective antagonist alpha-bungarotoxin (10(-7) M). Our results show that nicotinic receptor activation partially protects nigral dopaminergic neurons from 1-methyl-4-phenylpyridinium-induced toxicity in culture and that this appears to occur through an interaction at non-alpha7 containing receptors. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:275 / 285
页数:11
相关论文
共 78 条
[41]   Characterization of nicotinic receptors in immortalized hippocampal neurons [J].
Komourian, J ;
Quik, M .
BRAIN RESEARCH, 1996, 718 (1-2) :37-45
[42]   Parkinson's disease - Second of two parts [J].
Lang, AE ;
Lozano, AM .
NEW ENGLAND JOURNAL OF MEDICINE, 1998, 339 (16) :1130-1143
[43]   Parkinson's disease - First of two parts [J].
Lang, AE ;
Lozano, AM .
NEW ENGLAND JOURNAL OF MEDICINE, 1998, 339 (15) :1044-1053
[44]   Involvement of α6 nicotinic receptor subunit in nicotine-elicited locomotion, demonstrated by in vivo antisense oligonucleotide infusion [J].
Le Novère, N ;
Zoli, M ;
Léna, C ;
Ferrari, R ;
Picciotto, MR ;
Merlo-Pich, E ;
Changeux, JP .
NEUROREPORT, 1999, 10 (12) :2497-2501
[45]  
LeNovere N, 1996, EUR J NEUROSCI, V8, P2428
[46]   α7 Nicotinic receptor mediated protection against ethanol-induced cytotoxicity in PC12 cells [J].
Li, YX ;
King, MA ;
Grimes, J ;
Smith, N ;
de Fiebre, CM ;
Meyer, EM .
BRAIN RESEARCH, 1999, 816 (01) :225-228
[47]   Characterization of the neuroprotective and toxic effects of α7 nicotinic receptor activation in PC12 cells [J].
Li, YX ;
Papke, RL ;
He, YJ ;
Millard, WJ ;
Meyer, EM .
BRAIN RESEARCH, 1999, 830 (02) :218-225
[48]   Striatal increase of neurotrophic factors as a mechanism of nicotine protection in experimental parkinsonism [J].
Maggio, R ;
Riva, M ;
Vaglini, F ;
Fornai, F ;
Racagni, G ;
Corsini, GU .
JOURNAL OF NEURAL TRANSMISSION, 1997, 104 (10) :1113-1123
[49]  
Maggio R, 1998, J NEUROCHEM, V71, P2439
[50]  
MARKS MJ, 1983, J PHARMACOL EXP THER, V226, P817