| Project/Area Number |
18591301
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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 | Sapporo Medical University |
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Principal Investigator |
HASHIMOTO Eri Sapporo Medical University, Dept of Neuropsychiatry, Associate Professor (30301401)
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| Co-Investigator(Kenkyū-buntansha) |
UKAI Wataru Sapporo Medical University, Dept. of Neuropsychiatry, Assistant Professor (40381256)
IKEDA Hiroshi Hokkaido Bunkyo University, Faculty of Human Science, Professor (30232193)
YAMADA Misa National Center of Neurology and Psychiatry, Dept of Psychogeriatrics, Research Fellow (10384182)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | neuroscience / brain / depression / neural stem cell / antidepressant / neurogenesis / ER stress / cultured cell |
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| Research Abstract |
Many studies suggest the stressful events possibly promote neurochemical changes in the brain and induce the abnormality of neurogenesis that may be involved in the pathogenesis of depression. We previously have indicated the promotive effects of antidepressants on the neural stem cell (NSC) differentiation. In the present study, we investigated the effect of antidepressants on the NSC functional change induced by ER stress, and analyzed the cellular regulatory mechanism including the trophic factor signaling and NRSF which acts as a transcriptional repressor of neuronal genes in the terminal stage of NSC differentiation. We prepared NSCs from rat embryos and evaluated neuronal differentiation by using cell counting and ELISA. ER stress suppressed neuronal differentiation even at lower concentrations that did not affect the survival of NSCs. Antidepressants promoted neuronal differentiation of NSCs and reduced binding activity of NRSF against ER stress, while ERK signaling reduction decreased neuronal differentiation and activated NRSF binding activity. These results suggest that the alteration of NRSF binding activity through ER stress and/or ERK signaling underlies the mechanism of NSC dysfunction in depression and one of the critical cellular mechanisms of the effects of antidepressants. We also tried to visualize the transplanted NSCs in the brain of a psychiatric disease model rat using the marked NSCs. The transplanted cells were detected in wide areas of brain and were greater in number in the brains of the model rat group to the control group. With the cDNA microarray on which antidepressant related genes (ADRGs) were spotted, we found the expression of some of the ADRGs including ADRG#116 were related to neural differentiation and development. These results suggest some candidate genes and molecules as the novel therapeutic targets by activating intrinsic NSCs.
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