Possible role of neurogenesis of hippocampal dentate granule cells in the antagonistic mechanisms to development of epileptogenesis
| Project/Area Number |
13670847
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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 | Nippon Medical School |
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Principal Investigator |
MARU Eiichi Nippon Medical School, Associate Professor, 医学部, 助教授 (80221597)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGATA Kanato Tokyo Metropolitan Institute for Neuroscience, Director of Neuropharmacology Department, 東京都神経科学総合研究所・神経薬理, 副参事研究員 (20263262)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | amygdala kindling / epileptic seizures / hippocampal dentate gyrus / granule cell / neurogenesis / cell adhesion molecule / knockout mouse / arcadlin / 海馬顆粒細胞 / ストレス関連ホルモン / corticotropin-releasing factor(CRF) / CRF-binding protein ligand inhibitor |
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| Research Abstract |
Epileptic seizures significantly facilitate the neurogenesis of dentate granule cells in the adult hippocampus. It is a moot question whether the seizure-induced neurogenesis of granule cells aggravates epileptic seizures or it exerts an inhibitory effect on the development of epileptogenesis. We recently found that epileptic seizures also induce rapidly and transiently a novel cell adhesion molecule, arcadlin, in brain neurons, especially in dentate granule cells. In the present study, using wild-type and ardadlin-knockout mice, we examined possible role of the dentate neurogenesis in the kindling model of epilepsy and long-term synaptic potentiation (LTP) in the following three experiments.
(1) We examined the neurogenesis of granule cells in the dentate gyrus of adult arcadlin-knockout mice. It was found that arcadlin-kaockout mice had a significant reduction in number of newly born cells in the dentate gyrus and hilus compared with wild-type mice. The result clearly indicates arcadlin play a critical role in the proliferation of dentate gyrus precursor cells.
(2) We also examined the development of amygdala kindling in arcadlin-knockout mice. The rate of amygdala kindling development was significantly accelerated hi arcadlin-knockout mice compared with wild-type mice. Thus, it is quite possible that arcadlin exerts an antagonistic effect to development of epileptogenesis.
(3) Under urethane anesthesia, we examined the induction of at the perforant path-dentate granule cell synapses in arcadlin-knockout mice. It was found that the induction of LTP was seriously impaired in the dentate gyrus of arcadlin-knockout mice.
Because arcadlin-knockout mice in which the neurogenesis of dentate granule cells was significantly reduced showed the faster development of kindling, it is suggested that the neurogenesis of dentate granule cells play an inhibitory role in development of epileptogenesis.
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Report
(3 results)
Research Products
(9 results)
