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孕期暴露于丙戊酸致自闭症动物模型:行为改变和肝参数。

Animal model of autism induced by prenatal exposure to valproate: behavioral changes and liver parameters.

机构信息

Federal University of Rio Grande do Sul, Research Group in Neuroglial Plasticity, Porto Alegre, RS, Brazil.

出版信息

Brain Res. 2011 Aug 23;1408:8-16. doi: 10.1016/j.brainres.2011.06.015. Epub 2011 Jun 12.

Abstract

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.

摘要

自闭症的行为障碍主要表现在三个领域

社交互动、语言、沟通和想象力游戏以及兴趣和活动范围。这种综合征由于其高发病率而引起了社会的关注。产前暴露于丙戊酸(VPA)诱导的动物模型已被提出用于研究自闭症。在 VPA 大鼠中发现的一些行为异常特征,如重复/刻板样活动和社交互动缺陷,与自闭症有关。诱导大鼠的策略灵活性、社交记忆和代谢状态等特征尚未得到检查。因此,这项工作的主要目的是研究自闭症在啮齿动物行为上的其他相似性,以及产前暴露于 VPA 后肝脏的氧化还原参数。VPA 组的幼鼠表现出对陌生大鼠的异常接近、对同种大鼠的条件性位置偏好降低、正常的空间学习以及缺乏改变策略的灵活性。成年后,它们对陌生大鼠的社交方式不当,对社交新颖性的偏好降低,表面上的社交识别正常,没有空间学习缺陷。对 VPA 组肝脏的检查显示,过氧化氢酶(CAT)活性增加了 12%,超氧化物歧化酶(SOD)活性没有改变,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 的大鼠表现出策略灵活性降低和社交障碍,类似于自闭症症状,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。

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