一种尼古丁依赖行为的秀丽隐杆线虫模型：TRP家族通道的调节作用
A C. elegans model of nicotine-dependent behavior: regulation by TRP-family channels.
作者信息
Feng Zhaoyang, Li Wei, Ward Alex, Piggott Beverly J, Larkspur Erin R, Sternberg Paul W, Xu X Z Shawn
机构信息
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
出版信息
Cell. 2006 Nov 3;127(3):621-33. doi: 10.1016/j.cell.2006.09.035.
Nicotine, the primary addictive substance in tobacco, induces profound behavioral responses in mammals, but the underlying genetic mechanisms are not 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 for 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.
尼古丁是烟草中的主要成瘾物质，它能在哺乳动物中引发深刻的行为反应，但其潜在的遗传机制尚未完全明晰。在此，我们构建了一个依赖尼古丁行为的秀丽隐杆线虫模型。我们发现线虫对尼古丁的行为反应与在哺乳动物中观察到的相似，包括急性反应、耐受性、戒断反应和致敏作用。这些尼古丁反应需要烟碱型乙酰胆碱受体（nAChR）家族基因，已知这些基因在哺乳动物中介导尼古丁依赖，这表明nAChR在尼古丁反应中具有功能保守性。重要的是，我们发现缺乏瞬时受体电位经典型（TRPC）通道的突变线虫对尼古丁的反应存在缺陷，并且这种缺陷可被人类TRPC通道挽救，这揭示了TRPC通道在调节尼古丁依赖行为中出人意料的作用。因此，秀丽隐杆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。
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