The Study of Neuroprotection and Regeneration on Neurodegenerative Flatworm model using inverteverate Planarian

最近，研究表明鱼藤酮和1-甲基-4-苯基吡啶（MPP^+， MPTP的代谢物）抑制线粒体复合体I，是建立灵长类动物和啮齿动物等脊椎动物帕金森病模型的有用工具。涡虫是一种无脊椎扁虫，具有很高的再生潜力，多巴胺在其行为中起着关键作用。我们研究了一种克隆的涡虫，来自Dugesia japonica涡虫的GI菌株，用鱼藤酮或MPTP处理后，出现了浓度和时间依赖性的自溶和个体死亡。此外，鱼藤酮或MPTP诱导的这些作用被几种抗帕金森药物和半胱天冬酶抑制剂所抑制。这些结果表明，暴露于鱼藤酮和MPTP会导致多巴胺能功能障碍、帕金森样症状和半胱天冬酶依赖性死亡，甚至在扁虫、涡虫中也是如此。由于涡虫是比果蝇（Drosophila melanogaster）和线虫（Caenorhabditis elegans）更低等的无脊椎动物，从低等无脊椎动物到哺乳动物可能存在相同的多巴胺能神经元功能和caspase依赖通路。然而，在涡虫中发生的是DNA降解，而不是DNA断裂。因此，鱼藤酮或MPTP治疗的涡虫是一种新的帕金森扁平虫模型。

Recently, it has been shown that rotenone and 1-methyl-4-phenylpyridinium (MPP^+, a metabolite of MPTP), which inhibit mitochondrial complex I, are useful tools for parkinsonian models in vertebrates such as primates and rodents. Planarian, an invertebrate flatworm, has a high potential for regeneration, and dopamine plays a key role in its behavior. We examined a cloned planarian, the GI strain from Dugesia japonica Planarians that were treated with rotenone or MPTP underwent autolysis and individual death in a concentration- and time-dependent manner. In addition, these effects induced by rotenone or MPTP were inhibited by several antiparkinsonian drugs and caspase inhibitors. These results suggest that exposure to rotenone and MPTP causes dopaminergic dysfunction, parkinsonism-like symptoms and caspase-dependent death even in a flatworm, planarian. Since planarian is a lower invertebrate than fruit fly (Drosophila melanogaster) and nematode (Caenorhabditis elegans), common functions of dopaminergic neurons and caspase-dependent pathway(s) may exist from lower invertebrates to mammals. However, DNA degradation, rather than DNA fragmentation, occurred in planarian. Thus, planarian treated with rotenone or MPTP is a novel parkinsonian flatworm model.