| Project/Area Number |
16390310
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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 |
Embryonic/Neonatal medicine
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| Research Institution | The University of Tokushima |
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Principal Investigator |
FUKUI Yoshihiro The University of Tokushima, Graduate School Institute of Health Biosciences, Professor, 大学院ヘルスバイオサイエンス研究部, 教授 (50144168)
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| Co-Investigator(Kenkyū-buntansha) |
SAWADA Kazuhiko The University of Tokushima, Graduate School Institute of Health Biosciences, Associate Professor, 大学院ヘルスバイオサイエンス研究部, 助教授 (10284324)
SAKATA Hiromi (HAGA Hiromi) The University of Tokushima, Gradate School Institute of Health Biosciences, Assistant Professor, 大学院ヘルスバイオサイエンス研究部, 講師 (50294666)
IMAGAWA Tomohiro The University of Tokushima, School of Medecine, Associate Professor, 医学部, 助教授 (20232605)
MIKI Takanori The University of Tokushima, School of Medecine, Associate Professor, 医学部, 助教授 (30274294)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2005: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥7,300,000 (Direct Cost: ¥7,300,000)
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| Keywords | fetal alcohol syndrome / serotonin / BDNF / NGF / astrocyte / NFG / チロシン水酸化酵素 / FGF8 / TGFβ / GFAP / ビメンチン / Fetal alcohol syndrome / Dopamine / Serotonin / Shh / Hippocampus / Pyramidal cell |
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| Research Abstract |
To identify genes and factors which are responsible for brain alterations after prenatal ethanol exposure, we examined expression of genes and determination of neurotransmitters or neurotrophic factors in ethanol-exposed rat brains. Immunohistochemical study using anti-5-HT antibody revealed that prenatal ethanol exposure resulted in a reduction in the number and defects of migration of serotonin-positive neurons in the dorsal and medial raphe nuclei of rat fetuses. In ethanol-exposed rat fetuses, amounts of both 5-HT and its metabolite (5-HIAA) were decreased as well. RT-PCR analysis revealed a reduction of sonic hedgehog (Shh) expression in the brains of ethanol-exposed rat fetuses. Because Shh is related to the fate of 5-HT neuron, we concluded that prenatal exposure to ethanol impairs the development of 5-HT neurons, and this might have resulted in the reduction of Shh expressions. Therefore, the reduction of 5-HT neurons seen in the raphe persisted into adulthood, and prenatal ethanol-exposed rats showed anxiety-like behavior. In ethanol-exposed rat cerebellum, BDNF mRNA was decreased but NGF and its receptor (Trk A) mRNA expression were increased. Also, reduction of OMgp and GDNF mRNA expression was observed in the hippocampus and the septum nucleus, respectively. Thus, it is established that ethanol can affect expression of certain neurotrophic factors and their receptors. We monitored the intracellular calcium concentration after glutamate stimulation in ethanol-treated astrocytes derived from the hippocampus of neonatal rat (Day 3), and revealed that the glutamate-reactive cell number was decreased compared to non-ethanol-treated astrocytes. Since the calcium concentration in astrocytes might be related to maturation of synapse, the result suggests that ethanol may affect development of the neural circuit via a calcium signaling cascade in astrocytes.
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