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

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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.