2004 Fiscal Year Final Research Report Summary
Effects of PPARγ and its mew on the development of central nervous system.
| Project/Area Number |
15590227
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Osaka University |
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Principal Investigator |
WADA Koichiro Osaka University, Graduate School of Dentistry Pharmacology, Assistant Professor, 大学院・歯学研究科, 講師 (90263467)
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| Co-Investigator(Kenkyū-buntansha) |
KAMISAKI Yoshinori Osaka University, Graduate School of Dentistry Pharmacology, Professor, 大学院・歯学研究科, 教授 (40116017)
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| Project Period (FY) |
2003 – 2004
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| Keywords | PPARγ / Central nervous system / Neural stem cell / Proliferation / Lentiviral vector / Cell cycle / Apoptosis / Knockout mouse |
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| Research Abstract |
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.
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Research Products
(25 results)
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[Journal Article] RNA interfering approach for clarifying the PPARγ pathway using lentiviral vector expressing short hairpin RNA.2004
Author(s)
Katayama K, Wada K, Miyoshi H, Ohashi K, Tachibana M, Furuki R, Mizuguchi H, Hayakawa T, Nakajima A, Tsutsumi Y, Kadowaki T, Nakagawa S, Kamisaki Y, Mayumi T.
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Journal Title
FEBS Letters 560
Pages: 178-182
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A novel therapy for acute hepatitis utilizing Dehydroepiandrosterone in the murine model of hepatitis.2004
Author(s)
Yoneda M, Wada K, Katayama K, Nakajima N, Iwasaki T, Osawa E, Mukasa K, Yamada Y, Blumberg RS, Sekihara H, Nakajima A.
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Journal Title
Biochemical Pharmacology 68
Pages: 2283-2289
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Protective effect of endogenous PPARγ agonist acute gastric mucosal lesions associated with ischemia-reperfusion.2004
Author(s)
Wada K, Nakajima A, Takahashi H, Yoneda M, Fujisawa N, Ohsawa E, Kadowaki T, Kubota N, Terauchi Y, Matsuhashi N, Saubermann LJ, Nakajima N, Blumberg RS.
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Journal Title
American Journal of Physiology 287
Pages: G452-G458
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A novel PPARγ-gene therapy to control inflammation associated with inflammatory bowel disease in a murine model.2003
Author(s)
Katayama K, Wada K, Nakajima A, Mizuguchi H, Hayakawa T, Nakagawa S, Kadowaki T, Nagai R, Kamisaki Y, Blumberg RS, Mayumi T.
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Journal Title
Gastroenterology 124
Pages: 1315-1324
Description
「研究成果報告書概要(欧文)」より
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