| Project/Area Number |
08557146
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
SASA Masahi Hiroshima Univ.Sch.of Med., Professor, 医学部, 教授 (20025654)
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| Co-Investigator(Kenkyū-buntansha) |
NODA Atsushi Res.Inst.for Animal Sci.in Bio.and Toxicol.Chief Investigator, 毒性部, 室長
SEKIKAWA Tadao KyotoUniv, Faculty of Med.Professor, 医学部, 教授 (30025655)
MATSUBAYASHI Hiroaki Hiroshima Univ.Sch.of Med.Research Associate, 医学部, 助手 (60165850)
ISHIHARA Kumatoshi Hiroshima Univ.Sch.of Med.Assistant Professor, 医学部, 講師 (20212912)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | Noda epileptic rat (NER) / epileptic model animal / acoustic priming / audiogenic seizure / autosomal recessive gene / high-amplitude spike / depolarization shift / Ca^<2+> channel abnormality / ノダてんかんラット(NER) / 高振幅スパイク / 音誘発発作 / 強直-間代性けいれん / 高電位棘波群発 / カルシウムチャネル |
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| Research Abstract |
Studies were performed on the mutant, found in Crj-Wistar colony known as Noda epileptic rat (NER), tp determine whether or not the convulsions observed in it are epileptic seizures in order to establish the NER as an epileptic model that produces produces consistent and frequent seizures. NER displayd sudden jumping/running followed by tonic-clonic convulsions once per 30hr after 8-16wk of age. The seizures occured in 98% of NER after the F9 generation. Backcross studies revealed that the seizures were controlled by a major autosomal recessive gene.
Induction of more frequent and consistent convulsive seizures by acoustic priming was achieved by first exposing 3wk old animals for 30sec followed by weekly stimulation between 4 and 22 weeks of age to a bell derived acoustic stimulus of 95dB and 8KHz in 24 NERs and 15 control wistar rats. Audiogenic seizures were established in all animals examined after 9 weeks of age. The seizures were fundamentally identical to those occurring spontane
… More
ously. The cortical and hippocampal EEG depicted a low-voltage spike-wave with tonic convulsions which evolved into a high-amplitude spike- or polyspike-wave associated with clonic convulsions followed by a flattening or diffuse showing. In addition, sporadic spikes predominated in the hippocampus while spike-wave bursts occurred frequently in both the cortex and hippocampus at the interical stage from 11 and 20wk of age, respectively. Thus, audiogenic susceptibility in NER was successfully and consistently induced by acoustic priming, and the NER could probably serve as a new genetic model useful for experimental studies of human epilepsy. Furthermore, to elucidate the mechanism underlying the seizures in NER,electrophysiological studies with conventional intracellular recordings were performed using a slice preparation of the hippocampus. A single stimulus delivered to the mossy fibers elicited a long-lasting depolarization shift accompanying repetitive firing in the CA3 neurons. This abnormal response was completely blocked by the Ca^<2+> antagonist, nicardipine. These findings suggest that abnormal activities in the hippocampal CA3 neurons of NER may resemble those of SER in functions and characteristics. Less
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