摘要
Objective To investigate the toxic effect of environmental neurotoxin MPP^＋ to C.elegans and identify the mechanisms that cause the toxicity.Methods Humanα-synuclein transgenic C.elegans was used as the animal model,the toxic effect of MPP^＋ to dopamine（DA）neurons and the lifespan of worms was tested.The worms were feed with OP50 to determine whether ATP increase can rescue the worm from toxicity.ATP level and aberrant protein accumulation were analyzed in the MPP^＋ treated worms with or without OP50 addition.Results We found that MPP^＋ induced DA cell death and worm lethality,which could be prevented by OP50 treatment.OP50 exerted the protective effect by up-regulating ATP level,even though it also induced accumulation ofα-synuclein.Despite the undefined role of protein aggregation to the cell death,our results showed that the toxicity of MPP^＋ was mainly caused by the ATP depletion in theα-synuclein transgenic C.elegans.Conclusion MPP^＋ could induce DA neuronal death and worm lethality inα-synuclein transgenic C.elegans;Compared with the aggregation ofα-synuclein,the major cause of MPP^＋ toxicity appeared due to ATP depletion.
目的揭示环境神经毒素MPP^+对线虫的毒性影响并探讨其毒性机理。方法以人源α-synuclein转基因线虫作为动物模型,用MPP^+处理该线虫,观察MPP^+对线虫多巴胺能神经元和其生存能力的影响。通过供给OP50以提高线虫体内ATP的水平,对比分析ATP水平、蛋白质异常沉积等重要指标,探讨二者在MPP^+引起的转基因线虫的病变中所起的作用。结果MPP^+能够引起线虫多巴胺能神经元和线虫虫体的死亡;尽管进食OP50也会引起α-synuclein的沉积,但进食OP50能够提高体内ATP的水平并缓解MPP^+的毒性。虽无直接证据证明α-synuclein沉积对神经细胞的影响,但结果提示,在该转基因线虫中,与蛋白质的异常沉积相比,MPP^+导致的ATP损耗是其毒性作用的最主要诱因。结论MPP^+可以引起α-synuclein转基因线虫多巴胺能神经元的死亡和虫体的死亡,其毒性的主要原因是ATP损耗而不是α-synuclein的异常聚集(沉积)。
