Rose Jacqueline K, Miller Miranda K, Crane Stephanie A, Hope Kevin A, Pittman Paul G
Program in Behavioral Neuroscience and Department of Psychology, Western Washington University, 516 High St., Bellingham, WA, USA.
Neurotoxicol Teratol. 2013 Sep-Oct;39:122-7. doi: 10.1016/j.ntt.2013.07.007. Epub 2013 Jul 29.
Early nicotine exposure has been associated with many long-term consequences that include neuroanatomical alterations, as well as behavioral and cognitive deficits. To describe the effects of early nicotine exposure in Caenorhabditis elegans, the current study observed spontaneous locomotor activity (i.e., reversals) either in the presence or absence of nicotine. Expression of acr-16 (a nicotinic receptor subunit) and a β-like GABA(A) receptor subunit, gab-1, were also examined with RT-PCR. Worms were exposed to nicotine (30 μM) throughout "zygote formation" (period that includes oocyte maturation, ovulation and fertilization), from hatching to adulthood ("larval development") or across both zygote and larval development. Adult larval-exposed worms only showed an increase in spontaneous behavior when tested on nicotine (p<0.001) but levels of activity similar to controls when tested on plain plates (p>0.30). Larval-exposed worms also showed control levels of acr-16 nicotinic receptor expression (p>0.10) but increased gab-1 expression relative to controls (p<0.01). In contrast, zygote-exposed and zygote- plus larval-exposed worms showed a similar increase in spontaneous behavior on plain plates (p<0.001 and p=0.001, respectively) but control levels of responding when tested on nicotine (p>0.90 for each). However, expression of acr-16 and gab-1 was downregulated in zygote-exposed (p<0.01 and p<0.05, respectively) and significantly upregulated in the zygote- plus larval-exposed worms (p<0.000 for each); most surprising was the over five-fold increase in gab-1 expression. These results suggest that spontaneous motor behavior and receptor expression are differentially modulated by nicotine exposure during larval development and/or zygote formation. As well, these findings demonstrate that C. elegans, as a model system, is also sensitive to nicotine exposure during early development and provides the basis for future research to uncover specific mechanisms by which early nicotine exposure modifies neuronal signaling and alters behavior.
早期接触尼古丁与许多长期后果相关，包括神经解剖学改变以及行为和认知缺陷。为了描述早期接触尼古丁对秀丽隐杆线虫的影响，本研究观察了在有或没有尼古丁的情况下的自发运动活动（即转身次数）。还通过逆转录聚合酶链反应检测了acr-16（一种烟碱受体亚基）和β样GABA(A)受体亚基gab-1的表达。线虫在整个“合子形成”过程（包括卵母细胞成熟、排卵和受精阶段）、从孵化到成年（“幼虫发育”）或在合子和幼虫发育两个阶段都接触尼古丁（30μM）。仅在幼虫期接触尼古丁的成年线虫在尼古丁测试时仅表现出自发行为增加（p<0.001），但在普通平板上测试时活动水平与对照组相似（p>0.30）。幼虫期接触尼古丁的线虫还表现出acr-16烟碱受体表达水平与对照组相当（p>0.10），但相对于对照组gab-1表达增加（p<0.01）。相比之下，在合子期接触尼古丁的线虫以及在合子期和幼虫期都接触尼古丁的线虫在普通平板上表现出自发行为有类似增加（分别为p<0.001和p=0.001），但在尼古丁测试时反应水平与对照组相当（每组p>0.90）。然而，在合子期接触尼古丁的线虫中acr-16和gab-1的表达下调（分别为p<0.01和p<0.05），而在合子期和幼虫期都接触尼古丁的线虫中则显著上调（每组p<0.000）；最令人惊讶的是gab-1表达增加了五倍多。这些结果表明，幼虫发育和/或合子形成过程中接触尼古丁会对自发运动行为和受体表达产生不同程度的调节。此外，这些发现表明，秀丽隐杆线虫作为一种模型系统，在早期发育过程中对尼古丁接触也很敏感，并为未来研究揭示早期接触尼古丁改变神经元信号传导和行为的具体机制提供了基础。
