Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human α-synuclein
Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human α-synuclein
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DOI：
10.1046/j.1471-4159.2003.01809.x
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发表时间：
2003-07-01
影响因子：
4.7
通讯作者：
Wong, G
中科院分区：
文献类型：
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作者：
Lakso, M;Vartiainen, S;Wong, G
在包括培养的神经元、果蝇和小鼠的模型系统中，人α-突触核蛋白的过表达导致模拟包括帕金森病的突触核蛋白病的生化和病理变化。我们已经通过转基因注射到秀丽隐杆线虫中过表达野生型（WT）和突变丙氨酸53->苏氨酸（A53 T）人α-突触核蛋白。当WT或A53 T α-突触核蛋白用泛神经元或运动神经元启动子过表达时，观察到运动缺陷。在所有三组C.当人α-突触核蛋白在多巴胺能神经元或泛神经元启动子的控制下过表达时，而不是在运动神经元启动子的控制下，在过表达的WT和A53 T形式之间或在不同年龄（4天、10天或2周）的蠕虫之间，神经元损失没有显著差异。这些结果证明了人α-突触核蛋白在C.依赖于特定神经元亚型的表达。该转基因模型在C.秀丽线虫是一种无脊椎动物，具有进一步遗传操作的优良实验资源，可能有助于解剖各种突触核蛋白病的病理生理机制。
Overexpression of human alpha-synuclein in model systems, including cultured neurons, drosophila and mice, leads to biochemical and pathological changes that mimic synucleopathies including Parkinson's disease. We have overexpressed both wild-type (WT) and mutant alanine53-->threonine (A53T) human alpha-synuclein by transgenic injection into Caenorhabditis elegans . Motor deficits were observed when either WT or A53T alpha-synuclein was overexpressed with a pan-neuronal or motor neuron promoter. Neuronal and dendritic loss were accelerated in all three sets of C. elegans dopaminergic neurons when human alpha-synuclein was overexpressed under the control of a dopaminergic neuron or pan-neuronal promoter, but not with a motor neuron promoter. There were no significant differences in neuronal loss between overexpressed WT and A53T forms or between worms of different ages (4 days, 10 days or 2 weeks). These results demonstrate neuronal and behavioral perturbations elicited by human alpha-synuclein in C. elegans that are dependent upon expression in specific neuron subtypes. This transgenic model in C. elegans , an invertebrate organism with excellent experimental resources for further genetic manipulation, may help facilitate dissection of pathophysiologic mechanisms of various synucleopathies.