Sensitivity of zebrafish to environmental toxins implicated in Parkinson's disease
Sensitivity of zebrafish to environmental toxins implicated in Parkinson's disease
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DOI：
10.1016/j.ntt.2004.06.014
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发表时间：
2004-11-01
影响因子：
2.9
通讯作者：
Guo, S
中科院分区：
文献类型：
--
作者：
Bretaud, S;Lee, S;Guo, S
帕金森病（PD）的特征在于黑质中多巴胺能（DA）神经元的进行性损失和运动缺陷，包括运动迟缓、震颤和姿势不平衡。尽管PD的病因和发病机制仍然知之甚少，但动物模型研究提供了重要的见解。一种有价值的PD动物模型是通过用PD诱导神经毒素（包括1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）、鱼藤酮和百草枯）处理动物来建立的。这些神经毒素被认为抑制线粒体复合物I活性，导致氧化应激、能量代谢受损、蛋白酶体功能障碍，并最终导致多巴胺神经元损失。然而，这些药物神经毒性的基因和途径尚不清楚。在这项研究中，我们探讨了MPTP，鱼藤酮，百草枯在成年和幼虫斑马鱼，这是非常适合遗传分析，可以导致识别的潜在基因和途径的影响。在这里，我们报告说，成年斑马鱼显示行为改变，包括减少运动活动响应MPTP，而幼斑马鱼表现出发育，行为和DA敏感性，这些代理。综上所述，这些发现表明，斑马鱼可能是一个有价值的模型，从遗传学角度解剖PD诱导剂神经毒性的分子机制。(C)2004年爱思唯尔公司All rights reserved.
Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra and movement defects, including bradykinesia, tremor, and postural imbalance. Whereas the etiology and pathogenesis of PD is still poorly understood, studies in animal models are providing important insights. One valuable type of animal model for PD is established by treating animals with PD-inducing neurotoxins, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, and paraquat. These neurotoxins are thought to inhibit mitochondrial complex I activity leading to oxidative stress, impaired energy metabolism, proteasomal dysfunction, and, eventually, dopamine neuronal loss. However, the genes and pathways that underlie the neurotoxicity of these agents are not known. In this study, we explored the effect of MPTP, rotenone, and paraquat in both adult and larval zebrafish, which are highly amenable to genetic analysis that can lead to the identification of the underlying genes and pathways. Here, we report that adult zebrafish display behavioral alterations, including decreased locomotor activity in response to MPTP, whereas larval zebrafish exhibited developmental, behavioral, and DA sensitivity to these agents. Taken together, these findings suggest that zebrafish could be a valuable model for genetically dissecting the molecular mechanisms underlying the neurotoxicity of PD-inducing agents. (C) 2004 Elsevier Inc. All rights reserved.