Animal model of autism induced by prenatal exposure to valproate: Behavioral changes and liver parameters
Animal model of autism induced by prenatal exposure to valproate: Behavioral changes and liver parameters
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DOI：
10.1016/j.brainres.2011.06.015
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发表时间：
2011-08-23
期刊：
影响因子：
2.9
通讯作者：
Gottfried, Carmem
中科院分区：
文献类型：
--
作者：
Bambini-Junior, Victorio;Rodrigues, Leticia;Gottfried, Carmem
自闭症的特征是在三个主要领域的行为障碍：社会互动;语言，沟通和想象力的发挥;以及一系列的兴趣和活动。该综合征的高患病率引起了社会的广泛关注。产前暴露于丙戊酸（VPA）诱导的动物模型已被提议用于研究自闭症。在VPA大鼠中发现的行为异常的几个特征，如重复/刻板样活动和社会互动缺陷与自闭症相关。尚未检查诱导大鼠改变策略的灵活性、社会记忆和代谢状态等特征。因此，这项工作的主要目的是研究其他行为啮齿动物与自闭症的相似性，以及产前暴露于VPA后的肝脏氧化还原参数。VPA组的年轻大鼠对陌生大鼠表现出异常的接近，对同种大鼠的条件性位置偏好降低，空间学习正常，缺乏改变策略的灵活性。成年后，它们对陌生大鼠表现出不适当的社会接近，对社会新奇事物的偏好下降，社会识别明显正常，没有空间学习障碍。VPA组的肝脏检查显示过氧化氢酶（CAT）活性水平显著升高（12%），超氧化物歧化酶（SOD）活性无变化，SOD/CAT比值降低。TBARS、巯基和羰基含量以及血清转氨酶水平保持不变。总之，产前暴露于VPA的大鼠表现出改变策略的灵活性降低和类似于自闭症症状的社交障碍，有助于理解与自闭症谱系障碍相关的神经发育症状和氧化失衡。(C)出版社：Elsevier B. V.
Autism is characterized by behavioral impairments in three main domains: social interaction; language, communication and imaginative play; and range of interests and activities. This syndrome has attracted social attention by its high prevalence. The animal model induced by prenatal exposure to valproic acid (VPA) has been proposed to study autism. Several characteristics of behavioral abnormalities found in the VPA rats, such as repetitive/stereotypic-like activity and deficit in social interaction have been correlated with autism. Features like flexibility to change strategy, social memory and metabolic status of the induced rats have not been examined. Thus, the main aim of this work was to investigate additional behavioral rodent similarities with autism, as well as, liver redox parameters after prenatal exposure to VPA. Young rats from the VPA group presented aberrant approach to a stranger rat, decreased conditioned place preference to conspecifics, normal spatial learning and a lack of flexibility to change their strategy. As adults, they presented inappropriate social approach to a stranger rat, decreased preference for social novelty, apparently normal social recognition and no spatial learning deficits. Examination of the liver from the VPA group presented significantly increased (12%) levels of catalase (CAT) activity, no alteration in superoxide dismutase (SOD) activity and a decrease in the SOD/CAT ratio. TBARS, sulfhydril and carbonyl contents, and serum levels of aminotransferases remained unchanged. In summary, rats prenatally exposed to VPA presented decreased flexibility to change strategy and social impairments similar to the autism symptoms, contributing to the understanding of neurodevelopmental symptoms and oxidative imbalance associated to the autism spectrum disorder. (C) 2011 Published by Elsevier B.V.