Dasmahapatra Asok K, Carty Dennis R, Khan Ikhlas A
National Center for Natural Product Research, School of Pharmacy, University of Mississippi, University, MS, USA; Department of Biomolecular Sciences, Pharmacology Division, School of Pharmacy, University of Mississippi, University, MS, USA.
Department of Biomolecular Sciences, Environmental Toxicology Division, School of Pharmacy, University of Mississippi, University, MS, USA.
Chemosphere. 2017 Nov;186:901-910. doi: 10.1016/j.chemosphere.2017.08.048. Epub 2017 Aug 10.
Evidence indicated ethanol exposure during development disrupts brain functions that induces fetal alcohol spectrum disorder (FASD) phenotypes with behavioral abnormalities. We aimed to investigate whether prenatal ethanol exposure has any potential impact on behavior of a FASD fish model. Fertilized Japanese medaka (Oryzias latipes) eggs were exposed to 100-300 mM ethanol or 2 mM 5-azacytidine (5-azaC), 0-2 day post fertilization (dpf), in embryo-rearing medium (ERM). Survived embryos were maintained in clean ERM and used either for gene expression analysis on 2- and 6-dpf or allowed to hatch for behavioral study. Photomotor response of 3-4 day post hatch larvae were tracked for 3 h with light-dark transitions. It was observed that larval swimming was phototactic; enhanced in presence of light, declined in dark. Phototactic response was also observed in larvae prenatally exposed to ethanol or 5-azaC; however, the total distance swum by these larvae compared to controls declined. Further analysis indicated that, in light phases, total swimming activity and average swimming speed were reduced in larvae prenatally exposed to ethanol (300 mM) or 5-azaC. Expression analysis of baz1a and baz2a in embryos indicated developmental regulation. Ethanol (100-300 mM) or 5-azaC (2 mM) were able to modulate downregulation of both baz1a and baz2a mRNAs only in 6 dpf embryos of 300 mM ethanol and 5-azaC (2 mM) groups. These studies indicated that prenatal exposure to ethanol or 5-azaC was able to disrupt movements and thus swimming behavior in FASD phenotypes probably due to delayed remodeling of genome and epigenome.
有证据表明，发育过程中接触乙醇会扰乱大脑功能，从而诱发具有行为异常的胎儿酒精谱系障碍（FASD）表型。我们旨在研究产前接触乙醇是否会对FASD鱼类模型的行为产生任何潜在影响。将受精的日本青鳉（Oryzias latipes）卵在胚胎饲养培养基（ERM）中于受精后0 - 2天暴露于100 - 300 mM乙醇或2 mM 5-氮杂胞苷（5-azaC）。存活的胚胎在干净的ERM中饲养，并用于2日龄和6日龄时的基因表达分析，或者孵化后用于行为研究。对孵化后3 - 4天的幼虫进行3小时的明暗转换光运动反应追踪。观察到幼虫游泳具有趋光性；在有光时增强，在黑暗中下降。在产前暴露于乙醇或5-azaC的幼虫中也观察到趋光反应；然而，与对照组相比，这些幼虫的总游动距离下降。进一步分析表明，在光照阶段，产前暴露于乙醇（300 mM）或5-azaC的幼虫的总游泳活动和平均游泳速度降低。胚胎中baz1a和baz2a的表达分析表明存在发育调控。仅在300 mM乙醇和5-azaC（2 mM）组的6日龄胚胎中，乙醇（100 - 300 mM）或5-azaC（2 mM）能够调节baz1a和baz2a mRNA的下调。这些研究表明，产前暴露于乙醇或5-azaC可能由于基因组和表观基因组的重塑延迟而破坏FASD表型中的运动，进而扰乱游泳行为。
