2013 Fiscal Year Final Research Report
Impact of epileptic seizures on developing brain: a study using forebrain-specific Cdk5 conditional knockout mice
| Project/Area Number |
22591118
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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 |
Pediatrics
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
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| Project Period (FY) |
2010-04-01 – 2013-03-31
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| Keywords | てんかん / けいれん / 神経変性 / 炎症 / 皮質形成異常 / Cdk5 |
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| Research Abstract |
Neuronal migration disorders are often identified in patients with epilepsy refractory to medical treatment. The prolonged or repeated seizures are known to cause neuronal death; however, the mechanism remains to be elucidated. The objective of this study is to elucidate the impact of epileptic seizures on the developing brain using forebrain-specific Cdk5 knockout (Cdk5cKO) mice which show neuronal migration defects and seizures. The forebrain of the mice showed neurodegenerative changes accompanied by neuronal loss and microglial activation. Treatment with PPAR-gamma agonist pioglitazone ameliorated gliosis and neuronal loss in Cdk5cKO mice, suggesting that inflammation contributes to the pathogenesis of the seizure-induced neuronal death. This study may provide impetus for considering the development of anti-inflammatory therapies that can be used to avoid the progressive decline of neuronal function in patients with neuronal migration disorders and epilepsy.
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