The role of neuropeptide Y and its receptor subtypes in regulating the epileptogenesis of a novel epileptic rat : Noda epileptic rat.
| Project/Area Number |
11670941
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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 |
Psychiatric science
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
MASUI Akira Shiga University of Medical Science, School of Medicine, Research Associate., 医学部, 助手 (80190346)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Yoshinari Shiga University of Medical Science, School of Medicine, Research Associate., 医学部, 助手 (70303766)
加藤 進昌 滋賀医科大学, 分子神経科学研究センター, 客員教授 (10106213)
石田 展弥 滋賀医科大学, 医学部, 講師 (20159742)
金井 裕彦 滋賀医科大学, 医学部, 助手 (30293830)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | epilepsy / animal model / spontaneous seizure / neuropeptide Y / receptor / hippocampus / point mutation / モデル動物 / ノダ・てんかん・ラット / mRNA / in situ hybridization |
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| Research Abstract |
We assessed the possible relevance of neuropeptide Y (NPY) to the seizure susceptibility in Noda epileptic rat (NER), that is an epileptic mutant strain with spontaneous generalized tonic-clonic seizures (GTCS). We previously reported the continuous elevation of the NPY-like immunoreactivity in the hippocampus of NER matured enough to develop GTCS, and also reported a transient increase of NPY mRNA following a spontaneous GTCS in the dentate granule cell layer. In the present study, to elucidate the possible role of NPY receptor subtypes in spontaneous seizures of NER, we investigated NPY immunostaining and the changes in Y1, Y2 and Y5 receptor bindings and Y1 and Y2 receptor mRNA expressions after a spontaneous GTCS using receptor autoradiography and in situ hybridization. A marked increase of Y2 receptor binding in the hilus and of Y2 receptor mRNA in the dentate granule cells was observed after a GTCS.As commonly found in several other epileptic models, this result may indicate the role of Y2 receptors as an endogenous mechanism for quenching hyperexcitability in the hippocampus. In contrast, a spontaneous seizure of NER induced no Y1-receptor down-regulation as observed in other models of epilepsy using naive rats. Since NPY Y1 receptors are noted to mediate the excitatory action of NPY on dentate granule cells, this result may contribute to the seizure susceptibility of NER.
Furthermore, we screened the coding region of Y2 receptor gene of NER for mutations. There were two point mutations, which results in a non-conservative amino acid substitution ; 1) Leu-20-Phe at nucleotide position 58 (C to T) and 2) Thr-266-Met at position 266 (C to T). Whether these alleles contribute the function of Y2 receptor is still unclear.
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Report
(3 results)
Research Products
(6 results)
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[Publications] Jinde,S.,Masui,A.,Morinobu,S.,Takahashi,Y.,Tsunashima,K.,Noda,A.,Yamada,N.and Kato,N.: "Elevated neuropeptide Y and corticotropin-releasing factor in the brain Of a novel epileptic rat : Noda epileptic rat."Brain Research. 833. 286-290 (1999)
Description
「研究成果報告書概要(和文)」より
Related Report
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[Publications] Takahashi,Y.,Tsunashima,K.,Sadamatsu,M.,Schwarzer,S.,Amano,S.,Ihara,N.,Sasa,M.,Kato,N.,Sperk,G.: "Altered hippocampal expression of neuropeptide Y, somatostatin, and glutamate Decarboxylase in Ihara's epileptic rat and spontaneously epileptic rat."Neuroscience Letters. 287. 105-108 (2000)
Description
「研究成果報告書概要(和文)」より
Related Report
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[Publications] Jinde, S., Masui, A., Morinobu, S., Takahashi, Y., Tsunashima, K., Noda, A., Yamada, N.and Kato, N.: "Elevated neuropeptide Y and corticotropin-releasing factor in the brain of a novel epileptic rat : Noda epileptic rat."Brain Research. 833. 286-290 (1999)
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Publications] Takahashi, Y., Tsunahsima, K., Sadamatsu, M., Schwarzer, S., Amano, S., Ihara, N., Sasa, M., Kato, N.and Spark, G.: "Altered hippocampal expression of neuropeptide Y, somatostatin, and glutamate decarboxylase in Ihara's epileptic rat and spontaneously epileptic rat."Neuroscience Letters. 287. 105-108 (2000)
Description
「研究成果報告書概要(欧文)」より
Related Report
-
[Publications] Takahashi,Y.,Tsunashima,K.,Sadamatsu,M.,Schwarzer,S.,Amano,S., Ihara,N.,Sasa,M.,Kato,N.,Sperk,G.: "Altered hippocampal expression of neuropeptide Y, somatostatin, and glutamate Decarboxylase in Ihara's epileptic rat and spontaneously epileptic rat."Neuroscience Letters. 287. 105-108 (2000)
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