The critical period of valproate exposure to induce autistic symptoms in Sprague-Dawley rats
The critical period of valproate exposure to induce autistic symptoms in Sprague-Dawley rats
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DOI：
10.1016/j.toxlet.2010.12.018
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发表时间：
2011-03-05
影响因子：
3.5
通讯作者：
Ko, Kwang Ho
中科院分区：
文献类型：
--
作者：
Kim, Ki Chan;Kim, Pitna;Ko, Kwang Ho
胎儿暴露于丙戊酸（VPA）可诱导新生儿自闭症谱系障碍相关的神经管缺陷和社会行为障碍，使其成为一种有用的自闭症动物模型。本研究比较了Sprague-Dawley大鼠从胚胎第7天到胚胎第15天，不同时间窗的丙戊酸暴露对自闭症相关社会行为改变的影响，以确定自闭症相关社会行为改变的关键时期。与E7、E9.5和EIS暴露相比，VPA暴露在E12时的行为变化最显著，社会性和社会偏好降低。E9.5暴露于丙戊酸显示出强烈的生殖毒性，包括活产数量减少。一般来说，5度的暴露对生殖和社会行为只有边际影响。最后，暴露于vpa的大鼠在E12比暴露于vpa的大鼠在任何其他时期对电击更敏感。这些结果表明，E12是丙戊酸暴露对大鼠的社会行为改变具有显著影响的关键时期，与人类自闭症行为相似。2010爱思唯尔爱尔兰有限公司版权所有。
Prenatal exposure to valproic acid (VPA) induces neural tube defects and impairment in social behaviors related to autistic spectrum disorder in newborns, which make it a useful animal model of autism. In this study, we compared the effects of different time window of prenatal valproic acid exposure for inducing the altered social behaviors relevant to autism from embryonic day 7 to embryonic day 15 in Sprague-Dawley rats to determine the critical periods for the impairment. Compared to E7, E9.5 and EIS exposure, VPA exposure at E12 showed most significant changes in behaviors over control animals with reduced sociability and social preference. E9.5 exposure to valproic acid showed strong reproductive toxicity including decrease in the number of live birth. In general, exposure at El 5 showed only marginal effects on reproduction and social behaviors. Finally, VPA-exposed rats at E12 were more sensitive to electric shock than VPA-exposed rats at any other periods. These results suggested that E12 is the critical period in rats when valproate exposure has prominent effects for inducing the altered social behavior similar to human autistic behavior. (C) 2010 Elsevier Ireland Ltd. All rights reserved.