Developmental ethanol exposure causes central nervous system dysfunction and may slow the aging process in a Drosophila model of fetal alcohol spectrum disorder.
Developmental ethanol exposure causes central nervous system dysfunction and may slow the aging process in a Drosophila model of fetal alcohol spectrum disorder.
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发育中的乙醇暴露会导致中枢神经系统功能障碍，并可能减缓胎儿酒精谱系障碍果蝇模型的衰老过程。
DOI：
10.1016/j.alcohol.2021.03.006
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
French,RachaelL
中科院分区：
文献类型：
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作者：
Belhorma,Khaoula;Darwish,Nahed;Benn-Hirsch,Elizabeth;Duenas,Annalisa;Gates,Hillary;Sanghera,Navneet;Wu,Jodie;French,RachaelL
酒精是一种已知的致畸因素，发育过程中接触酒精会导致胎儿酒精谱障碍(FASD)。出生时患有FASD的儿童会出现一系列症状，包括出生体重低、小头畸形和神经行为问题。据估计，仅在美国，FASD患者每年的治疗费用就高达40亿美元，每个受影响的人一生中要花费200万美元。我们建立了黑腹果蝇作为研究FASD的模式生物。在这里，我们报告了果蝇阿尔茨海默病相关蛋白TMCC2的同源基因Dementin(Dmtn)的突变，表达了对发育中酒精暴露的敏感性，并提供了乙醇干扰Dmtn表达的证据。此外，我们发现，用乙醇饲养的果蝇表现出轻微的爬行缺陷，提示神经退化。令人惊讶的是，我们的数据还表明，用乙醇饲养的果蝇比对照动物衰老得更慢，我们发现一些衰老缓慢的突变体对发育中的酒精暴露很敏感。最后，我们发现，以乙醇喂养的果蝇显示出编码抗氧化酶的基因持续上调，这可能有助于减缓中枢神经系统的衰老速度。因此，除了已有文献记载的发育期酒精暴露对神经系统的负面影响外，成年动物可能还存在先前未被怀疑的神经保护作用。
Alcohol is a known teratogen, and developmental exposure to ethanol results in fetal alcohol spectrum disorder (FASD). Children born with FASD can exhibit a range of symptoms including low birth weight, microcephaly, and neurobehavioral problems. Treatment of patients with FASD is estimated to cost 4 billion dollars per year in the United States alone, and 2 million dollars per affected individual's lifetime. We have establishedDrosophila melanogasteras a model organism for the study of FASD. Here we report that mutations inDementin (Dmtn), theDrosophilaortholog of the Alzheimer's disease-associated protein TMCC2, convey sensitivity to developmental ethanol exposure, and provide evidence thatDmtnexpression is disrupted by ethanol. In addition, we find that flies reared on ethanol exhibit mild climbing defects suggestive of neurodegeneration. Surprisingly, our data also suggest that flies reared on ethanol age more slowly than control animals, and we find that a number of slow-aging mutants are sensitive to developmental ethanol exposure. Finally, we find that flies reared on ethanol showed a persistent upregulation of genes encoding antioxidant enzymes, which may contribute to a reduced rate of central nervous system aging. Thus, in addition to the well-documented negative effects of developmental alcohol exposure on the nervous system, there may be a previously unsuspected neuroprotective effect in adult animals.