Molecular biological approach to explore the cause of brain damage after prenatal ethanol exposure

分子生物学方法探讨产前乙醇暴露后脑损伤的原因

• 批准号: 16390310
• 负责人: FUKUI Yoshihiro
• 金额: $ 8.51万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390310/
• 关键词: 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

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.

为了确定导致产前乙醇暴露后大脑变化的基因和因素，我们检查了乙醇暴露大鼠大脑中的基因表达和神经递质或神经营养因子的测定。使用抗 5-HT 抗体的免疫组织化学研究表明，产前乙醇暴露导致大鼠胎儿中缝背核和中缝核中血清素阳性神经元的数量和迁移缺陷减少。在暴露于乙醇的大鼠胎儿中，5-HT 及其代谢物 (5-HIAA) 的含量也有所减少。 RT-PCR 分析显示，暴露于乙醇的大鼠胎儿大脑中音猬因子 (Shh) 的表达减少。由于Shh与5-HT神经元的命运相关，我们得出结论，产前接触乙醇会损害5-HT神经元的发育，这可能导致Shh表达减少。因此，中缝中5-HT神经元的减少持续到成年期，并且产前乙醇暴露的大鼠表现出焦虑样行为。在乙醇暴露的大鼠小脑中，BDNF mRNA 减少，但 NGF 及其受体 (Trk A) mRNA 表达增加。此外，在海马和隔膜核中分别观察到 OMgp 和 GDNF mRNA 表达的减少。因此，确定乙醇可以影响某些神经营养因子及其受体的表达。我们监测了来自新生大鼠海马的经乙醇处理的星形胶质细胞（第3天）谷氨酸刺激后的细胞内钙浓度，结果发现与未经乙醇处理的星形胶质细胞相比，谷氨酸反应细胞数量减少。由于星形胶质细胞中的钙浓度可能与突触的成熟有关，因此结果表明乙醇可能通过星形胶质细胞中的钙信号级联影响神经回路的发育。

项目成果

女性とアルコール

妇女和酒精

• 发表时间: 2005
• 作者: Mochizuki S;Mizukami H;Ogura T;Kure S;Ichinohe A;Kojima K;Matsubara Y;Kobayashi E;Okada T;Hoshika A;Ozawa K;Kume A;坂田 ひろみ
• 通讯作者: 坂田 ひろみ

Oligodendrocyte myelin glycoprotein (OMgp) in rat hippocampus is depleted by chronic ethanol consumption.

大鼠海马中的少突胶质细胞髓磷脂糖蛋白（OMgp）因长期乙醇消耗而耗尽。

• 发表时间: 2006
• 期刊: Neurosci Lett. 406
• 作者: Okamoto H;et al.
• 通讯作者: et al.

Effects of chronic ethanol administration on the expression levels of neurotrophic factors in the rat hippocampus.

慢性乙醇给药对大鼠海马神经营养因子表达水平的影响。

• 发表时间: 2006
• 期刊: Okajimas Folia Anat Jpn. 83
• 作者: Okamoto H;et al.
• 通讯作者: et al.

Morphological study on the inferior olivary nuclear complex of the donkey (Equus asinus)

驴下橄榄核复合体的形态学研究

• 发表时间: 2006
• 期刊: Tisssue and Cell 38
• 作者: RASHED R;et al.
• 通讯作者: et al.

Interaction between glycogen body cell and neuron : examination in co-culture system

糖原体细胞和神经元之间的相互作用：共培养系统中的检查

• 发表时间: 2006
• 期刊: Journal of Veterinary Medical Science 68(in press)
• 作者: Imagawa T;et al.
• 通讯作者: et al.