| Project/Area Number |
14370292
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Sapporo Medical University |
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Principal Investigator |
SAITO Toshikazu Sapporo Medical Univ, Neuropsy School of Medicine, Professor, 医学部, 教授 (50128518)
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| Co-Investigator(Kenkyū-buntansha) |
SOHMA Hitoshi Sapporo Medical Univ, Dept of Biochem School of Medicine, Assisant Professor, 医学部, 助教授 (70226702)
YAMAMOTO Megumi Sapporo Medical Univ, Neuropsy School of Medicine, 医学部, 助手 (90347170)
OZAWA Hiroki Nagasaki Univ, Division of Neuropsy Dept of Neurosensory Medicine, Professor, 医学部, 教授 (50260766)
KATO Tadafumi Riken Brain Science Institute, Dept of Molecular Dynamics of Mental Disorders, Laboratory Head, 精神疾患動態研究チーム, チームリーダー (30214381)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2003: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 2002: ¥8,500,000 (Direct Cost: ¥8,500,000)
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| Keywords | Alcohol dependence / cAMP / AnnexinIV / CREB / NE-κB / BDNF / Neurotrophic factor / Neural stem cell / アルコール依存 / c-AMP / アルコール / Ca^<2+> / Ca^<2+>-結合蛋白質 / NFκB / SH-SY5Y細胞 |
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| Research Abstract |
We have previously demonstrated that the cellular cAMP-signaling is changed in blood cells in family-history positive alcoholic patients : quantitative reduction of type 1 adenylyl cyclase(AC1), ACVIII and G_<sα> mRNA. Since the cellular Ca^<2+> signaling alternation by the chronic alcohol consumption has been attended as well as cAMP signaling, we investigated the effect of alcohol on the Ca^<2+> signaling, using postmortem human brains and cultured cells. The Ca^<2+>-binding protein, annexinIV was increased in the alcoholic patients, and the level of annexinIV was increased in alcohol-treated A549 cells. The cellular downstream signaling molecule of cAMP,cAMP responsive element binding protein(CREB) helps to regulate long-term potentiation and synaptic plasticity, it is plausible that EtOH affects the CREB-induced gene transcriptions, which may affect neural differentiation/development. We focused on the mechanism of the EtOH induced cell damage and examined the role of the neurotrop
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hic factor on the effect of EtOH with neurobalstoma cells(SH-SY5Y). The cellular damage was induced by Ethanol treatment in dose-dependently. The CREB activity and the secretion of brain-derived neurotrophic factor(BDNF) which expression is regulated by CREB were both diminished in the ethanol treated SH-SY5Y cells. On the other hand, the transcriptional activity of NF-κB was activated by Ethanol. These are demonstrated that the decrased CREB-BDNF pathway impairment and NE-κB activation are involved in the mechanisms of Ethanol induced damage and neuronalplasticity change. We next investigated the effects of EtOH on neuronal differentiation in neural stem cells(NSCs). EtOH(20 to 100mM) inhibited neuronal differentiation, without affecting survival rate. The addition, of either IGF-1 or BDNF diminished inhibitory effect of EtOH on NSC differentiation. Thus, it is suggested that neurotrophic factors play important roles not only in differentiation but also defense from EtOH-induced cellular damage. Less
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