The alteration of adult neural network by pre/post-natal alcohol and addictive drug exposure
| Project/Area Number |
16390327
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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 |
Psychiatric science
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
SAITO Toshikazu Sapporo Medical Univ, Dept of Neuropsy, Professor, 医学部, 教授 (50128518)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Hiroshi Sapporo Medical Univ, Dept of Neuropsy, Assistant Professor, 医学部, 講師 (30232193)
HASHIMOTO Eri Sapporo Medical Univ, Dept of Neuropsy, Assistant Professor, 医学部, 講師 (30301401)
SOHMA Hitoshi Sapporo Medical Univ, Dept of Bioengineering, Assistant Professor, 医学部, 助教授 (70226702)
YAMAMOTO Megumi Sapporo Medical Univ, Dept of Neuropsy, Assistant Professor, 医学部, 講師 (90347170)
KATO Tadafumi Riken Brain Institute, Aging and Psychiatric Research Group, Group Director, 老化・精神疾患研究グループ, グループディレクター (30214381)
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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 |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2005: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2004: ¥8,600,000 (Direct Cost: ¥8,600,000)
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| Keywords | alcohol damage / neural stem cell / fetal alcohol syndrome / neurogenesis / regenerative medicine / BDNF / NRSF / REST / CREB / エタノール / 神経栄養因子 / MAP2 / リン酸化Akt / リン酸化Erk |
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| Research Abstract |
We analyzed cellbiological change of damaged brain by prenatal and young adult ethanol exposure, focusing on the alteration of neural network maintenance function. First, we investigated the effect of ethanol on the Ca^<2+> signaling and Ca^<2+> binding protein using cultured cells and animal models and demonstrated pivotal role of NF-kB activation and CREB reduction on the impairment of premature neuronal cell development and mature neuron survival. We next proceeded the analysis of molecular mechanism of brain neural network change by ethanol using cultured neural stem cells derived from fetal rat brain, and revealed that ethanol decreased neural stem cell differentiation to neurons, but promoted their differentiation to astrocytes and to oligodendrocytes dose dependently. These were indicated that the reduction of neurotrophic factor signaling and activation of transcriptional suppressor NRSF/REST play an important role on the neural stem function change induced by ethanol. In the additional experiment, we demonstrated the decrease activity of neural stem cell proliferation and increase of gliogenesis in cultured neural stem cells derived from the fetal alcohol syndrome model. It was also indicated that the differentiation of neural stem cells derived from the model, sensitively decreased by the 2nd time ethanol exposure. These results strongly suggest that prenatal exposure of ethanol can induce neural stem cell function impairment in fetus brain, and might cause serious incidence on the neural network abnormal development of children's brain.
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Report
(3 results)
Research Products
(19 results)
