2017 Fiscal Year Final Research Report
Development of a new translational medicine for epilepsy using the Pten-mutant mice
| Project/Area Number |
15K09624
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中別府 雄作 九州大学, 生体防御医学研究所, 教授 (30180350)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | Pten / てんかん / 自閉症 / PI3-AKT-mTOR経路 / 治療 / 海馬 / ノックアウトマウス / Crh-POMC(ACTH) |
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| Outline of Final Research Achievements |
In the present study, we have generated conditional knockout mice that lacked expression of Pten in the Pomc-expressing neurons in the developing brain. All of these mice started showing generalized seizures from 8-9 weeks of age and died by 11 weeks of age. Biochemical studies and microscopic observation detected the age-dependent hypertrophy and dysmorphic appearance of the hippocampal dentate gyrus. We have also found that excitatory-inhibitory and Crh-Pomc (ACTH) unbalances became prominent in the dentate gyrus before the onset of seizures. We confirmed that the treatment with rapamycin prevented the onset of seizures and premature death of Pten-mutant mice. These data provide evidence that PI3K-AKT-mTOR is a molecular pathway that can be a therapeutic target for intractable epilepsy in future medicine.
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| Free Research Field |
小児神経学
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