| Project/Area Number |
16591147
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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 |
IKEDA Hiroshi Sapporo Med. Univ. Sch. Med., Dept. Neuropsychiatry, Assistant Prof., 医学部, 講師 (30232193)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Toshikazu Sapporo Med. Univ. Sch. Med., Dept. Neuropsychiatry, Professor, 医学部, 教授 (50128518)
HASHIMOTO Eri Sapporo Med. Univ. Sch. Med., Dept. Neuropsychiatry, Assistant Prof., 医学部, 講師 (30301401)
SOHMA Hitoshi Sapporo Med. Univ. Sch. Med., Dept. Neuropsychiatry, Associate Prof., 医学部, 助教授 (70226702)
UKAI Wataru Sapporo Med. Univ. Sch. Med., Dept. Neuropsychiatry, Instuructor, 医学部, 助手 (40381256)
YAMAMOTO Megumi Sapporo Med. Univ. Sch. Med., Dept. Neuropsychiatry, Assistant Prof., 医学部, 講師 (90347170)
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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 | ethanol / neural stem cell / NRSF / REST / ERK / BDNF / Akt / 神経新生 / 増殖 / 分化 / BDNF / IGF-1 / Lithium |
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| Research Abstract |
The purpose of this study was to elucidate the relationship between prenatal or early developmental exposure of the brain to ethanol and cognitive and behavioral disturbances observed after adolescence. We assumed such disturbances in behavior or cognition might be caused by alternation of neural network which was already started at prenatal or early developmental phase. Because neural stem cells (NSCs) play a pivotal role in the development and maturation of the central nervous system, it seems to be important to understand the effect of ethanol on underlying mechanisms that regulate NSC differentiation in the developing brain. In this study, we investigated the effects of ethanol on differentiation of NSC to neural cells and glial cells. To clarify the underlying mechanisms of the effects, we examined the signal transduction system involved in the regulation of NSC differentiation.
The results were followings ; 1)Ethanol inhibited NSC differentiation at concentrations much lower than what compromised neuronal survival. 2)Ethanol exposure increased astrocytic and oligocytic differentiation at the concentration as same above. 3)Ethanol-induced differential inhibition was reduced by both IGF-1 and BDNF. 4)Western blot analysis revealed that ethanol suppressed phosphorylation of ERK without affecting expression of total ERK. 5)Ethanol enhanced NRSF binding activity measured by the method based on the principal of electrophoretic mobility sift assay.
These results implicated that physiological concentration of ethanol affects on actively differentiated NSC in the developing brain, then these cause the alteration of neural network system. This study is possible to make a contribution to elucidation of underlying mechanisms of the harmful consequences of drinking during pregnancy.
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