Effects of PPARγ and its mew on the development of central nervous system.

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Most self-renewal in the central nervous system is dependent upon neural stem cells (NSCs) that are multi-potent and self-renewing progenitor cells. NSCs are expected to be of utility in the treatment of neurodegenerative disorders, such as Parkinson's disease, Huntington's disease, and multiple sclerosis. However, detailed mechanisms that control proliferation and differentiation of NSCs are still unclear. Therefore, we investigated the effects of various molecules that potentially affect the NSC proliferation and differentiation.We found high-level expression of PPARγ in embryo mouse brain and NSCs. In contrast, extremely low levels were observed in adult mouse brain. Inhibition of PPARγ pathway by specific antagonist or lentiviral vector-siRNA caused apoptosis of NSCs. Homozygous PPARγ-knockout mice showed disorder of the development of central nervous system. Those results indicate the importance of PPARγ pathway on the NSC proliferation and the development of central nervous system.We also investigated the effects of endocrine disruptors (EDs) or non-steroidal anti-inflammatory drugs (NSAIDs) on the proliferation of NSCs, because the both of them are closely related with the field of dentistry potentially affect the NSC proliferation. Diclofenac, but not other NSAIDs, caused apoptosis of NSCs. Nonylphenol, one of the EDs, also caused apoptosis of NSCs. Cell cycle arrest was involved in the mechanisms of both apoptosis.Together with those results, various molecules, such as PPARγ, EDs, and NSAIDs, affect the proliferation or differentiation of NSCs, and may influence the development of central nervous system.