Analysis of the molecular bases on the stress sensitivity and abnormal emotional function in the developmental process of Fyn-deficient mice.
| Project/Area Number |
17591130
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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 | National Center of Neurology and Psychiatry |
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Principal Investigator |
YUASA Shigeki National Institute of Neuroscience, Department of Ultrastructural Research, Director, 神経研究所 微細構造研究部, 部長 (70127596)
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| Co-Investigator(Kenkyū-buntansha) |
HATTORI Kotaro National Institute of Neuroscience, Department of Ultrastructural Research, Section chief, 微細構造研究部, 室長 (50415569)
ITOH Masayuki National Institute of Neuroscience, Department of Mental Retardation and Birth Defect, Section chief, 疾病研究第2部, 室長 (50243407)
NAKAHIRA Eiko National Institute of Neuroscience, Department of Ultrastructural Research, Postdoctral fellow, 微細構造研究部, 流動研究員 (10392432)
SOMA Miho National Institute of Neuroscience, Department of Ultrastructural Research, Postdoctral fellow, 微細構造研究部, 流動研究員 (70328756)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Fyn tyrosine kinase / neuronal migration / amygdala / striatum / emotion / NMDA receptor / in utero electroporation / cDNA array / 神経新生 / マイクロダイセクション / エレクトロポレーション |
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| Research Abstract |
The molecular mechanisms of defective emotional functions and neural development as found in the Fyn-tyrosine-kinase-deficient mice were investigated as a model for developmental disorders based on the distinct molecular defect. The defective neocorticogenesis, abnormal response to anti-psychotics and the defective function of amygdala were mainly analysed as well as the developmental mechanisms of amygdala.
1. Functional analysis of Fyn in the neocorticogenesis: the formation of the layers II-III was demonstrated to be defective in the Fyn deficiency, and the expression of Fyn was made clear to well correspond to the stage of generation and migration of the layer II-III neurons. The transfer of fyn gene into the neuroepithelium of the neocortical primordium of Fyn deficiency by in utero electroporation at the stage of neurogenesis of the layers II-III partially rescued the defective migration and stratification of the cortical neurons. The involvement of focal adhesion kinase in the Fy
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n-signal transduction pathway was also demonstrated in the process of neocorticogenesis.
2. Functional analysis of Fyn in the striatum: Fyn deficiency displays abnormal response to the administration of anti-psychotics such as haloperidol, a dopamine D2 receptor antagonist. In vivo and in vitro analysis revealed that haloperidol activates Fyn, and activated Fyn stimulates the tyrosine-phosphorylation of NMDA receptor NR2B subunit, subsequently enhancing the channel activity of NMDA receptor and the excitability of the striatal neurons.
3. Functional analysis of Fyn in the amygdala: since abnormal response to NMDA administration is found in the amygdala of Fyn deficiency, comprehensive analysis on the difference of gene expression in the amygdala between the control and Fyn deficiency was carried out following NMDA administration. Based on the laser capture micro-dissection and cDNA array analysis revealed that Swim6 gene was significantly down regulated in the amygdalar central nucleus of Fyn deficiency. I t was suggested that Swim6 is functionally coupled to MAPK signal transduction pathway. Less
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Report
(3 results)
Research Products
(16 results)
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[Journal Article] Altered gene expression in the subdivisions of the amygdala of Fyn-deficient mice as revealed by laser capture microdissection and mKIAA cDNA array analysis.2006
Author(s)
Kai N, Iwase K, Imai K, Nakahira E, Soma M, Ohtsuka S, Yagi T, Kobayashi K, Koga H, Takiguchi M, Yuasa S
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Journal Title
Brain Research 1073-1074
Pages: 60-70
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Altered gene expression in the subdivisions of the amygdala of Fyn-deficient mice as revealed by laser capture microdissection and mKIAA cDNA array analysis.2006
Author(s)
Kai N, Iwase K, Imai K, Nakahira E, Soma M, Ohtsuka S, Yagi T, Kobayashi K, Koga H, Takiguchi M, Yuasa S.
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Journal Title
Brain Research 1073-1074
Pages: 60-70
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Altered gene expression in the subdivision of the amygdala of Fyn-deficient mice as revealed by laser capture microdissection and mKIAA cDNA array analysis.2006
Author(s)
Kai, N., Iwase, K., Imai, K., Nakahira, E., Soma, M., 他5名, Yuasa, S.
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Journal Title
Brain Research 1073-1074
Pages: 60-70
Related Report
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[Journal Article] Fyn is required for haloperidol-induced catalepsy in mice.2006
Author(s)
Hattori, K., Uchino, S., Isosaka, T, 他3名, Kohsaka, S., Yagi, T., Yuasa, S.
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Journal Title
Journal of Biological Chemistry 281・11
Pages: 7129-7135
Related Report
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