| Project/Area Number |
16591148
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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, Assistant Prof., 医学部, 講師 (30301401)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Toshikazu Sapporo Medical University, Dept. of Neuropsychiatry, Professor, 医学部, 教授 (50128518)
SOHMA Hitoshi Sapporo Medical University, Dept. of Biomedical Engineering, Associate Prof., 医学部, 助教授 (70226702)
IKEDA Hiroshi Sapporo Medical University, Dept. of Neuropsychiatry, Assistant Prof., 医学部, 講師 (30232193)
YAMAMOTO Megumi Sapporo Medical University, Dept. of Neuropsychiatry, Assistant Prof., 医学部, 講師 (90347170)
UKAI Wataru Sapporo Medical University, Dept. of Neuropsychiatry, Instructor, 医学部, 助手 (40381256)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | neural stem cell / antidepressant / mood stabilizer / depression / neural network / cultured cell / transplantation / 移植 |
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| Research Abstract |
It has recently been hypothesized that depression could be relevant to a disturbance in neuronal plasticity, especially neurogenesis, and thus the maintenance and repair of the damaged neural network is a possible mechanism of the action of antidepressant and mood stabilizer treatment, as well as the pathophysiology of mood disorders. In the present study, we investigated the effects of antidepressants and mood stabilizers on proliferation, migration and differentiation of neural stem cells (NSCs) prepared from E-13.5 rat embryos, and analyzed the influence on survival of mature neurons. Both antidepressants and mood stabilizers showed promotive effects on the differentiation of NSCs into neurons. Mood stabilizers significantly promoted the survival of NSCs, while antidepressants showed no significant effect. We next examined a role for intracellular signal transduction pathways and the regulation of specific target genes by transcriptional factors in psychotropic drug treatments to identify the specific mechanism that influences the function of NSCs. The treatment of NSCs with antidepressants activated MEK/ERK signaling, while the treatment of NSCs with mood stabilizers activated PI3K/Akt signaling. These results suggest that the different potential of NSC differentiation and neuronal survival by the antidepressants and mood stabilizers relate to their differences of clinical response, and that the alterations of trophic factor signaling such as ERK and Akt play a key role in the promoting activity of neuronal differentiation and survival. Furthermore, we tried to analyze the in vivo mechanisms of neural network reconstruction, using NSCs transplantation system in the experimental model of psychiatric disease. The accumulation and distribution of transplanted cells were detected in subventricular zone and dentate gyrus of hippocampus in the model rat brain.
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