2000 Fiscal Year Final Research Report Summary
Possible role of neuropeptides in the establishment of epileptic forcus and the induction of febrile seizures
| Project/Area Number |
11670800
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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, Depatment of Physiology, Associate Professor, 医学部, 助教授 (80221597)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGATA Kanato Tokyo Metropolitan Institute For Neurosciences, Department of Neuropharmacology, Director, 東京都神経科学総合研究所, 副参事研究員 (20263262)
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| Project Period (FY) |
1999 – 2000
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| Keywords | febrile seizures / the establishment of epileptic focus / kindling / corticotropin-releasing factor (CRF) / CRF type I receptor / prostaglandin / kindling-induced synaptic potentiation (KIP) / long-term potentiation (LTP) |
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| Research Abstract |
Epileptic seizures have been shown to increase markedly the mRNA expression of corticotropin-releasing factor (CRF) and cyclooxygenase-2 (COX-2, the rate-limiting enzyme in prostaglandin synthesis) in the hippocampal dentate area. It was demonstrated, furthermore, that CRF injection into the cerebral ventricles produced severe limbic seizures especially in infant rats, and a non-specific CRF receptor antagonist, α-helical CRF, increased the threshold rectal temperature for febrile seizures. These results suggest that CRF and prostaglandin may play an important role in the establishment of epileptic focus and the induction of febrile seizures. Therefor, in the present study, we examined possible involvement of CRF type I receptors and prostaglandin in febrile seizures and the neuronal plasticity associated with epileptic seizures.
1. An intraperitoneal injection of CRF type I receptor antagonist, CRA1000, at a dose of 20 mg/kg slightly increased the threshold rectal temperature for febri
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le seizure induction from 42.4±0.7℃ to 42.9±1.4℃, but the increase in the threshold temperature is not statistically significant.
2. It has been shown that the synaptic transmission in the hippocampal dentate area was significantly potentiated by kindled seizures. CRA1000 (10 mg/kg, i.p.) had no effect on the postictal EPSP depression and the subsequent kindling-induced synaptic potentiation in adult rats.
3. High-frequency electrical stimulation inducing no epileptic seizure can produce another type of synaptic potentiation, the long-term synaptic potentiation (LTP), which was shown to facilitate the subsequent kindling development. CRA1000 (10 mg/kg, i.p.) had also no significant effect on LTP.
These results indicate that CRF type I receptor activation is not involved in the induction of febrile seizures and the epileptic neuronal plasticity.
4. COX-2 knockout mice and COX-2 selective inhibitor (nimesulide) -administered mice showed the enhancement of the postseizure inhibition. The result suggests that brain prostaglandin decrease the strength of postseizure inhibition and facilitate the recurrence of seizures. Less
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