Preventive effects of 5-HT agonists on the abnormal development of of 5-HTergic system induced by prenatal ethanol exposure in rats

5-HT激动剂对产前乙醇暴露所致大鼠5-HT能系统异常发育的预防作用

• 批准号: 23591595
• 负责人: FUKUI Yoshihiro
• 金额: $ 3.41万
• 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 (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591595/
• 关键词: 先天異常; セロトニン; 5-HT1A受容体作動薬; 5-HT２A/2C受容体作動薬; 脳発達; エタノール; ラット; 中脳縫線核; 5-HT2A/2c受容体; 脳発達期; 5-ＨＴ

We administered the 5-HT1A agonist, ipsapirone, or the 5-HT2A/2C agonist, DOI, against prenatal ethanol (EtOH)-exposed rats during E13-20. Based on our immunohistochamical observation on E20, administrations of both agonists prevented a reduction in the number of 5-HTergic neurons in the midbrain raphe nuclei induced by EtOH exposure during E10-20. Ipsapirone also alleviated an abnormality of anxiety-like behavior seen in an elevated-plus maze test caused by prenatal EtOH exposure. The quantitative analysis of gene expression in fetal brains revealed that an expression of Phox2b, which is related to development of 5-HT neurons, was reduced after prenatal exposure to EtOH, but DOI attenuated the effect of EtOH on Phox2b gene expression. We concluded that the effect of prenatal EtOH exposure on development of 5-HT neurons and behavioral changes resulting in the altered 5-HTergic systems could be alleviated by the enhancement of signaling via 5-HT1A or 5-HT2A/2C receptors during E13-20.

我们在 E13-20 期间对产前乙醇 (EtOH) 暴露的大鼠施用 5-HT1A 激动剂伊沙匹隆或 5-HT2A/2C 激动剂 DOI。根据我们对 E20 的免疫组织化学观察，两种激动剂的给药都阻止了 E10-20 期间 EtOH 暴露诱导的中脑中缝核中 5-HTergic 神经元数量的减少。 伊沙匹隆还缓解了因产前乙醇暴露引起的高架正迷宫测试中出现的焦虑样行为异常。对胎儿大脑中基因表达的定量分析表明，与 5-HT 神经元发育相关的 Phox2b 表达在产前暴露于 EtOH 后降低，但 DOI 减弱了 EtOH 对 Phox2b 基因表达的影响。我们得出的结论是，产前 EtOH 暴露对 5-HT 神经元发育和导致 5-HTergic 系统改变的行为变化的影响可以通过在 E13-20 期间增强 5-HT1A 或 5-HT2A/2C 受体的信号传导来减轻。

项目成果

Preventive effect of a 5-HT2A/2C receptor agonist on the reduction of serotonergic neurons induced by prenatal exposure to ethanol in rats

5-HT2A/2C受体激动剂对产前乙醇暴露引起的大鼠血清素能神经元减少的预防作用

• 发表时间: 2013
• 作者: Tsukasa Ishiguro,Hiromi Sakata-Haga;Yoshihiro Fukui
• 通讯作者: Yoshihiro Fukui

5-HT2A/2C受容体アゴニスト投与による胎生期エタノール曝露ラットの中脳縫線核5-HT神経細胞減少の抑制

给予5-HT2A/2C受体激动剂抑制产前乙醇暴露大鼠中脑中缝核5-HT神经元丢失

• 发表时间: 2013
• 作者: 石黒司;坂田ひろみ;福井義浩
• 通讯作者: 福井義浩

Prenatal ethanol exposure impairs passive avoidance acquisition and enhances unconditioned freezing in rat offspring

产前乙醇暴露会损害大鼠后代的被动回避获得并增强无条件冻结

• 发表时间: 2012
• 期刊: Behavioural Brain Research
• 影响因子: 2.7
• 作者: Ken-ichi Ohta;Hiromi Sakata-Haga;Yoshihiro Fukui
• 通讯作者: Yoshihiro Fukui

5-ＨＴ2Ａ/2Ｃ受容体アゴニスト投与による胎生期エタノール曝露ラットの中脳縫線核5-HT神経細胞減少の抑制

给予5-HT2A/2C受体激动剂抑制产前乙醇暴露大鼠中脑中缝核5-HT神经元丢失

• 发表时间: 2013
• 作者: 石黒 司;坂田 ひろみ;福井 義浩
• 通讯作者: 福井 義浩

Preventive effect of a 5-HT 2A/2C receptor agonist of the reduction of serotonergic neurons induced by prenatal exposure ethanol in rats

5-HT 2A/2C 受体激动剂对产前暴露乙醇引起的大鼠血清素能神经元减少的预防作用

• 发表时间: 2013
• 作者: Tsukasa Ishiguro;Hiromi Sakata-Haga;Yoshihiro Fukui
• 通讯作者: Yoshihiro Fukui