Basic and clinical research of mood disorder in light of neural signal transduction
| Project/Area Number |
17591222
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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 | Nagasaki University |
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Principal Investigator |
OZSAWA Hiroki Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (50260766)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANE Hideyuki Nagasaki University, Graduate School of Biomedical Sciences, Assistant Professor, 大学院医歯薬学総合研究科, 助教授 (90274795)
ITOH Tsutomu Nagasaki University, Graduate School of Biomedical Sciences, Lecturer, 大学院医歯薬学総合研究科, 講師 (40363501)
穴見 公隆 国立精神・神経センター, 武蔵病院神経科, 医長 (20415574)
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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: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | mood disorders / signal transduction / stem cell / antidepressants / cAMP / BDNF / Cilostazol |
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| Research Abstract |
Previously, we have reported that decreased activity of cAMP signaling was found in mood disorder's brain samples, and antidepressants activate cAMP signaling by changing the G protein functions. It is reported that activation of cAMP-PKA system regulates MAP kinase and PI 3-kinase pathway, which known to the major signaling cascades of trophic factors (IGF-1, BDNI), in the surviving process of mature neurons. Recently, the p-CREB expression in immature neurons was reported, and upregulation of cAMP induced increase the proliferation of newborn cells in adult rat hippocampus. However, the role and mechanisms of cAMP signals in the neural stem cell (NSC) differentiation have not yet been elucidated.
In the present study, we tried clinical application of cAMP enhancer cilostazol (phosihodieseterase type III inhibitors) for vascular depression. Cilostazol improve senile vascular depressives in time dependently. Serum BDNF is increased accompanied by clinical improvement. Additionally, we developed a quantitative and stable in vitro assay system to evaluate the neural stem cell proliferation using WST-8 assay. Here, we evaluated the effects of cilostazol in proliferation of neural sphere in vitro. In our experiment system, The cilostazol promoted proliferation of neural stem cells in almost clinically effective doses. Since it is well suggested that cAMP and PLC signaling pathway is a common target for antidepressants and cAMP enhancer, the detailed examination of the changes of cAMP-CREB/PLC-CREB system and trophic factor signaling in NSCs by the treatment of cAMP ehnhance is required.
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Report
(3 results)
Research Products
(30 results)
