Uncoupling nicotine mediated motoneuron axonal pathfinding errors and muscle degeneration in zebrafish.
Uncoupling nicotine mediated motoneuron axonal pathfinding errors and muscle degeneration in zebrafish.
复制标题
解偶联尼古丁介导的斑马鱼运动神经元轴突寻路错误和肌肉退化。
DOI：
10.1016/j.taap.2008.06.025
复制
发表时间：
2009
影响因子：
3.8
通讯作者：
Svoboda,KurtR
中科院分区：
文献类型：
--
作者：
Welsh,Lillian;Tanguay,RobertL;Svoboda,KurtR
斑马鱼胚胎提供了一个独特的机会来研究尼古丁暴露影响早期脊椎动物发育的机制。暴露于尼古丁的胚胎在42 hpf下功能瘫痪，这表明暴露于尼古丁的胚胎的神经肌肉系统受到损害。我们先前证明，尼古丁暴露的胚胎中的次级脊髓运动神经元发育延迟，并且它们的轴突产生寻路错误（Svoboda，K.，Vijayaraghaven，S.，Tanguay，R.L.，2002.尼古丁受体介导暴露于尼古丁的胚胎斑马鱼脊髓运动神经元发育和轴突寻路的变化。神经科学杂志22，10731-10741）。在该研究中，我们没有考虑尼古丁暴露引起的骨骼肌发育改变在脊髓运动神经元轴突寻路错误中可能发挥的潜在作用。在这项研究中，我们表明，骨骼肌发育的改变发生在脊髓运动神经元发育的改变后，暴露于尼古丁。肌肉中的改变涉及尼古丁与肌肉特异性AChR的结合。尼古丁诱导的肌肉发育改变不会发生在斑马鱼突变体（沙发土豆，[sop]）中，它缺乏功能性肌肉特异性AChRs。即使肌肉发育不受尼古丁暴露的sop突变体，运动神经元轴突寻路错误仍然发生在这些突变体，表明尼古丁暴露对神经系统发育的直接影响。
Zebrafish embryos offer a unique opportunity to investigate the mechanisms by which nicotine exposure impacts early vertebrate development. Embryos exposed to nicotine become functionally paralyzed by 42 hpf suggesting that the neuromuscular system is compromised in exposed embryos. We previously demonstrated that secondary spinal motoneurons in nicotine-exposed embryos were delayed in development and that their axons made pathfinding errors (Svoboda, K., Vijayaraghaven, S., Tanguay, R.L., 2002. Nicotinic receptors mediate changes in spinal motoneuron development and axonal pathfinding in embryonic zebrafish exposed to nicotine. J. Neurosci. 22, 10731–10741). In that study, we did not consider the potential role that altered skeletal muscle development caused by nicotine exposure could play in contributing to the errors in spinal motoneuron axon pathfinding. In this study, we show that an alteration in skeletal muscle development occurs in tandem with alterations in spinal motoneuron development upon exposure to nicotine. The alteration in the muscle involves the binding of nicotine to the muscle-specific AChRs. The nicotine-induced alteration in muscle development does not occur in the zebrafish mutant (sofa potato, [sop]), which lacks functional muscle-specific AChRs. Even though muscle development is unaffected by nicotine exposure in sop mutants, motoneuron axonal pathfinding errors still occur in these mutants, indicating a direct effect of nicotine exposure on nervous system development.