A 5-HT2A/2C receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, mitigates developmental neurotoxicity of ethanol to serotonergic neurons
A 5-HT2A/2C receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, mitigates developmental neurotoxicity of ethanol to serotonergic neurons
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DOI：
10.1111/cga.12152
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发表时间：
2016-07-01
影响因子：
1.3
通讯作者：
Fukui, Yoshihiro
中科院分区：
文献类型：
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作者：
Ishiguro, Tsukasa;Sakata-Haga, Hiromi;Fukui, Yoshihiro
胎儿期乙醇暴露导致中脑中缝核中5-HT能神经元减少。在本研究中，我们研究了在胎儿期通过5-HT 2A和5-HT 2C受体激活信号传导是否能够防止产前乙醇暴露诱导的5-HT能神经元减少。妊娠Sprague-Dawley大鼠在妊娠日（GD）10 - 20（Et）给予含2.5 - 5.0%（w/v）乙醇的流质饮食。作为配对喂养的对照，其他妊娠大鼠喂养相同的液体饮食，除了乙醇被等热量的蔗糖（Pf）取代。Et和Pf组又分为两组，其中一组用1 mg/kg（i. p.）1-（2，5-二甲氧基-4-碘苯基）-2-氨基丙烷（DOI），一种5-HT 2A/2C受体激动剂（Et-DOI或Pf-DOI），在GD 13 - 19期间注射，另一种仅注射生理盐水载体（Et-Sal或Pf-Sal）。在GD 19或20通过剖宫产取出其胎仔，并收集胎仔脑。使用色氨酸羟化酶抗体对胚胎第20天的胎儿中的5-HT能神经元进行免疫组织学检查，结果显示，与Pf-Sal和Pf-DOI胎儿相比，Et-Sal胎儿中脑中缝核中的5-HT能神经元数量显著减少，而Et-DOI和每个Pf对照之间无显著差异。因此，我们的结论是，减少5-HTergic神经元，导致产前乙醇暴露，可以减轻通过5-HT 2A/2C受体在胎儿期的信号增强。
Prenatal ethanol exposure causes the reduction of serotonergic (5-HTergic) neurons in the midbrain raphe nuclei. In the present study, we examined whether an activation of signaling via 5-HT2A and 5-HT2C receptors during the fetal period is able to prevent the reduction of 5-HTergic neurons induced by prenatal ethanol exposure. Pregnant Sprague-Dawley rats were given a liquid diet containing 2.5 to 5.0% (w/v) ethanol on gestational days (GDs) 10 to 20 (Et). As a pair-fed control, other pregnant rats were fed the same liquid diet except that the ethanol was replaced by isocaloric sucrose (Pf). Each Et and Pf group was subdivided into two groups; one of the groups was treated with 1mg/kg (i.p.) of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), an agonist for 5-HT2A/2C receptors, during GDs 13 to 19 (Et-DOI or Pf-DOI), and another was injected with saline vehicle only (Et-Sal or Pf-Sal). Their fetuses were removed by cesarean section on GD 19 or 20, and fetal brains were collected. An immunohistological examination of 5-HTergic neurons in the fetuses on embryonic day 20 using an antibody against tryptophan hydroxylase revealed that the number of 5-HTergic neurons in the midbrain raphe nuclei was significantly reduced in the Et-Sal fetuses compared to that of the Pf-Sal and Pf-DOI fetuses, whereas there were no significant differences between Et-DOI and each Pf control. Thus, we concluded that the reduction of 5-HTergic neurons that resulted in prenatal ethanol exposure could be alleviated by the enhancement of signaling via 5-HT2A/2C receptors during the fetal period.