期刊
JOURNAL OF NEUROSCIENCE RESEARCH
卷 87, 期 2, 页码 576-585出版社
WILEY
DOI: 10.1002/jnr.21869
关键词
Parkinson's disease; rotenone; nicotine; dopaminergic neuron; neuroprotection
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Japan Society for the Promotion of Science, Ministry of Health, Labour and Welfare of Japan
- Smoking Research Foundation
- Philip Morris USA Inc.
- Philip Morris International
Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic (DA) neuronal cell loss in the substantia nigra. Although the entire pathogenesis of PD is still unclear, both environmental and genetic factors contribute to neurodegeneration. Epidemiologic studies show that prevalence of PD is lower in smokers than in nonsmokers,. Nicotine, a releaser of dopamine from DA neurons, is one of the candidates of antiparkinson agents in tobacco. To assess the protective effect of nicotine against rotenone-induced DA neuronal cell toxicity, we examined the neuroprotective effects of nicotine in rotenone-induced PD models in vivo and in vitro. We observed that simultaneous subcutaneous administration of nicotine inhibited both motor deficits and DA neuronal cell loss in the substantia nigra of rote none-treated mice. Next, we analyzed the molecular mechanisms of DA neuroprotective effect of nicotine against rotenone-induced toxicity with primary DA neuronal culture. We found that DA neuroprotective effects of nicotine were inhibited by dihydro-beta-erythroidine (DH beta E), alpha-bungarotoxin (alpha BuTx), and/or PI3K-Akt/PKB (protein serine/threonine kinase B) inhibitors demonstrating that rotenone-toxicity on DA neuron's are inhibited via activation of alpha 4 beta 2 or alpha 7 nAChRs-PI3K-Akt/PKB pathway or pathways. These results suggest that the rotenone mouse model may be useful for assessing candidate antiparkinson agents, and that nAChR (nicotinic acetylcholine receptor) stimulation can protect DA neurons against degeneration. (C) 2008 Wiley-Liss, Inc.
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