A C-elegans model of nicotline-dependent behavior:: Regulation by TRP-family channels
A C-elegans model of nicotline-dependent behavior:: Regulation by TRP-family channels
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DOI：
10.1016/j.cell.2006.09.035
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发表时间：
2006-11-03
期刊：
影响因子：
64.5
通讯作者：
Xu, X. Z. Shawn
中科院分区：
文献类型：
--
作者：
Feng, Zhaoyang;Li, Wei;Xu, X. Z. Shawn
尼古丁是烟草中的主要成瘾物质，它能诱导哺乳动物产生深刻的行为反应，但其潜在的遗传机制尚不清楚。在这里，我们开发了一个C。尼古丁依赖行为的elegans模型。我们发现，蠕虫表现出的行为反应，尼古丁在哺乳动物中观察到的，包括急性反应，耐受性，戒断和致敏。这些尼古丁反应需要已知在哺乳动物中介导尼古丁依赖的烟碱乙酰胆碱受体（nAChR）家族基因，这表明nAChR在尼古丁反应中的功能保守。重要的是，我们发现缺乏TRPC（瞬时受体电位典型）通道的突变蠕虫在对尼古丁的反应中存在缺陷，并且这种缺陷可以被人类TRPC通道拯救，揭示了TRPC通道在调节尼古丁依赖行为中的意想不到的作用。因此，C.线虫可用于表征已知基因以及鉴定调节尼古丁反应的新基因。
Nicotine, the primary addictive substance in tobacco, induces profound behavioral responses in mammals, but the underlying genetic mechanisms are riot well understood. Here we develop a C. elegans model of nicotine-dependent behavior. We show that worms exhibit behavioral responses to nicotine that parallel those observed in mammals, including acute response, tolerance, withdrawal, and sensitization. These Nicotine responses require nicotinic acetylcholine receptor (nAChR) family genes that are known to mediate nicotine dependence in mammals, suggesting functional conservation of nAChRs in nicotine responses. Importantly, we find that mutant worms lacking TRPC (transient receptor potential canonical) channels are defective in their response to nicotine and that such a defect can be rescued by a human TRPC channel, revealing an unexpected role or TRPC channels in regulating nicotine-dependent behavior. Thus, C. elegans can be used to characterize known genes as well as to identify new genes regulating nicotine responses.