2010 Fiscal Year Final Research Report
Comprehensive research of MMP gene in an animal model of epileptic seizure
| Project/Area Number |
21790068
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Nagoya University |
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Principal Investigator |
MIZOGUCHI Hiroyuki Nagoya University, 環境医学研究所, 助教 (70402568)
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| Project Period (FY) |
2009 – 2010
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| Keywords | MMP / BDNF / てんかん / キンドリング / 海馬 |
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| Research Abstract |
In the present study, we investigated the role of matrix metalloproteinase (MMP)-9 in the development of pentylenetetrazole (PTZ)-induced kindled seizure in mice. Repeated treatment with PTZ (40 mg/kg) produced kindled seizure, which was accompanied by enhanced MMP-9 activity and expression in the hippocampus. No change in MMP-9 activity was observed in the hippocampi of mice with generalized tonic seizure following single administration of PTZ (60 mg/kg). MMP-9 colocalized with the neuronal marker NeuN and the glial marker GFAP in the dentate gyrus of the kindled mouse hippocampus. Coadministration of diazepam or MK-801 with PTZ inhibited the development of kindling and the increased MMP-9 levels in the hippocampus. Marked suppression of kindled seizure progression in response to repeated PTZ treatment was observed in MMP-9^<(-/-)> mice compared with wild-type mice, an observation that was accompanied by decreased hippocampal levels of mature brain-derived neurotrophic factor (BDNF) despite similar BDNF mRNA levels. These findings suggest that MMP-9 is involved in progression of behavioral phenotypes in kindled mice owing to conversion of pro-BDNF to mature BDNF in the hippocampus.
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