統合失調症の二重衝撃仮説(Two hit hypothesis)の証明
Project/Area Number |
18659333
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Research Category |
Grant-in-Aid for Exploratory Research
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Allocation Type | Single-year Grants |
Research Field |
Psychiatric science
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Research Institution | Osaka University |
Principal Investigator |
松崎 秀夫 Osaka University, 医学系研究科, 特任准教授(常勤) (00334970)
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Co-Investigator(Kenkyū-buntansha) |
中村 和彦 浜松医科大学, 医学部附属病院, 講師 (80263911)
土屋 賢治 浜松医科大学, 医学部, 助教 (20362189)
杉原 玄一 浜松医科大学, 医学部, 助教 (70402261)
岩田 泰秀 浜松医科大学, 医学部, 助教 (10285025)
関根 吉統 浜松医科大学, 医学部, 助手 (70324358)
|
Project Period (FY) |
2006 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2007: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
|
Keywords | 統合失調症 / 二重衝撃仮説 / GAD67 |
Research Abstract |
本課題は,統合失調症の「二重衝撃仮説(Two hit hypothesis)」の証明を目的とする。これは遺伝因としての「First hit(第一衝撃)」が統合失調症の脆弱性を形成し,ついで環境因としての「Second hit(第二衝撃)」が加わって統合失調症が発症する,とする仮説である。 昨年度まで、我々は子宮内胎児仮死経験ラットに認められる(1)メタンフェタミン投与後の移所行動量亢進,(2)海馬のBrdU陽性細胞数減少,(3)海馬の顆粒細胞数減少、の知見を得て、第34回日本脳科学会での発表を行った(現在投稿準備中)。この成果から,GAD67ノックアウトマウス(GAD67(+/-))に第二衝撃としての子宮内胎児仮死を経験させる実験を試みたが,子宮内仮死を経験することによってマウスがほとんど死んでしまったため,子宮内仮死について実験条件を再び検討した。その結果,現在のプロトコールをマウスに適用してモデルを作成することは困難との結論に至り,プロトコールを改善しても再現性のある実験結果が得られなかったため,本研究補助を受ける年度内に子宮内胎児仮死経験マウスを作ることを事実上断念した。 GAD67遺伝子改変マウスの再解析では,行動量の日内変動,ドパミン作動薬(メタンフェタミン)による移所行動量,PPI,社会的行動(Social Interaction)に有意な変化が認められなかった。さらに現在所有する動物実験設備下ではGAD67遺伝子改変マウスの交配・出生の効率が悪いこともあり,今後の行動実験に十分なマウスの提供ができない見通しも判明した。 以上の理由により,本研究計画を本年度内限りで中止することを決定した。
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Report
(2 results)
Research Products
(23 results)
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[Journal Article] Decreased expression of reelin receptor VLDLR in peripheral lymphocytes of drug-naive schizophrenic patients.2008
Author(s)
Suzuki K, Nakamura K, Iwata Y, Sekine Y, Kawai M, Sugihara G, Tsuchiya KJ, Suda S, Matsuzaki H, Takei N, Hashimoto K, Mori N.
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[Journal Article] Gene and expression analyses reveal enhanced expression of pericentrin 2 (PCNT2) in bipolar disorder.2008
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Anitha A, Nakamura K, Yamada K, Iwayama Y, Toyota T, Takei N, Iwata Y, Suzuki K, Sekine Y, Matsuzaki H, Kawai M, Miyoshi K, Katayama T, Matsuzaki S, Baba K, Honda A, Hattori T, Shimizu S, Kumamoto N, Tohyama M, Yoshikawa T, Mori N.
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Biological Psychiatry (In press)
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[Journal Article] Genetic analyses of Roundabout (ROBO) axon guidance receptors in autism.2008
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Anitha A, Nakamura K, Yamada K, Suda S, Thanseem I, Tsujii M, Iwayama Y, Hattori E, Toyota T, Miyachi T, Iwata Y, Suzuki K, Matsuzaki H, Kawai M, Sekine Y, Tsuchiya K, Sugihara GI, Ouchi Y, Sugiyama T, Koizumi K, Higashida H, Takei N, Yoshikawa T, Mori N.
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American Journal of Medical Genetics Part B: Neuropsychiatric Genetics (In press)
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[Journal Article] Genetic analyses of the brain-derivedneurotrophic factor (BDNF) gene in autism.2007
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Nishimura K, Nakamura K, Anitha A, Yamada K, Tsujii M, Iwayama Y, Hattori E, Toyota T, Takei N, Miyachi T, Iwata Y, Suzuki K, Matsuzaki H, Kawai M, Sekine Y, Tsuchiya K, Sugihara G, Suda S, Ouchi Y, Sugiyama T, Yoshikawa T, Mori N.
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Biochemical and Biophysical Research Communication 356(1)
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[Journal Article] Disruption of Reelin signaling attenuates methamphetamine-induced hyperlocomotion.2007
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Matsuzaki H, Minabe Y, Nakamura K, Suzuki K, Iwata Y, Sekine Y, Tsuchiya KJ, Sugihara G, Suda S, Takei N, Nakahara D, Hashimoto K, Nairn AC, Mori N, Sato K.
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Pages: 3376-84
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[Journal Article] SNP analyses of growth factor genes EGF, TGF-β1, and HGF revealhaplotypic association of EGF with autism.2007
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Toyoda T, Nakamura K, Yamada K, Thanseem I, Anitha A, Suda S, Tsujii M, Iwayama Y, Hattori E, Toyota T, Miyachi T, Iwata Y, Suzuki K, Matsuzaki H, Kawai M, Sekine Y, Tsuchiya K, Sugihara GI, Ouchi Y, Sugiyama T, Takei N, Yoshikawa T, Mori N.
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Biochemical and Biophysical Research Communication 360(4)
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[Journal Article] Decreased serum levels of transforming growth factor-beta1 in patients with autism.2007
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Okada K, Hashimoto K, Iwata Y, Nakamura K, Tsujii M, Tsuchiya KJ, Sekine Y, Suda S, Suzuki K, Sugihara G, Matsuzaki H, Sugiyama T, Kawai M, Minabe Y, Takei N, Mori N
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Progress in Neuro-Psychopharmacology and Biological Psychiatry 31(1)
Pages: 187-190
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[Journal Article] Increased levels of serum soluble L-selectin in unmedicated patients with schizophrenia.2007
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Iwata Y, Suzuki K, Nakamura K, Matsuzaki H, Sekine Y, Tsuchiya KJ, Sugihara G, Kawai M, Minabe Y, Takei N, Mori N
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Journal Title
Schizophrenia Research 89(1-3)
Pages: 154-160
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[Journal Article] Linkage disequilibrium analysis of the CHRNA7 gene and its partially duplicated region in schizophrenia.2007
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Iwata Y, Nakajima M, Yamada K, Nakamura K, Sekine Y, Tsuchiya KJ, Sugihara G, Matsuzaki H, Suda S, Suzuki K, Takei N, Mori N, Iwayama Y, Takao H, Yoshikawa T, Riley B, Makoff A, Sham P, Chen R, Collier D
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Neuroscience Research 57(2)
Pages: 194-202
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[Journal Article] Decreased serum levels of hepatocyte growth factor in male adults with high-functioning autism.2007
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Progress in Neuro-Psychopharmacology and Biological Psychiatry 31(2)
Pages: 412-415
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[Journal Article] Decreased serum levels of epidermal growth factor in adult Subjects with high-functioning autism.2007
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Biological Psychiatry (in press)
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[Journal Article] Decreased serum levels of PECAM-1 in subjects with high-functioning autism : a negative correlation with head circumference at birth.2007
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Tsuchiya KJ, Hashimoto K, Iwata Y, Tujii M, Sekine Y, Sugihara G, Matsuzaki H, Suda S, Kawai M, Nakamura K, Minabe Y, Yagi A, Iyo M, Takei N, Mori N
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Biological Psychiatry (in press)
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[Journal Article] An association study between COMT gene polymorphism and methamphetamine psychotic disorder.2006
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Suzuki A, Nakamura K, Sekine Y, Minabe Y, Takei N, Suzuki K., Iwata Y, Kawai M, Takebayashi K, Matsuzaki H, Iyo M, Ozaki N, Inada T, Iwata N, Harano M, Komiyama T, Yamada M, Sora I, Ujike H, Mori N
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[Journal Article] Increased serum levels of glutamate in adult patients with autism.2006
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[Presentation] Neurogenesis correlates sensorimotor gating via activation of hippocampal Akt2007
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Matsuzaki H, Wakuda T, Iwata Y, Seki N, Suzuki K, Suda S, Takei N, Tohyama M, Mori N
Organizer
The 37th annual meeting Society for Neuroscience
Place of Presentation
San Diego, CA, USA
Year and Date
2007-11-06
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