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自闭症幼鼠模型中丙戊酸盐治疗后的感觉和运动特征。

Sensory and motor characterization in the postnatal valproate rat model of autism.

机构信息

Department of Occupational Therapy, Virginia Commonwealth University, Richmond, VA 23298, USA.

出版信息

Dev Neurosci. 2012;34(2-3):258-67. doi: 10.1159/000336646. Epub 2012 May 24.

Abstract

Although autism is diagnosed according to three core features of social deficits, communication impairments, and repetitive or stereotyped behaviors, other behavioral features such as sensory and motor impairments are present in more than 70% of individuals with autism spectrum disorders (ASD). Exposure of rat pups to the teratogen valproate during sensitive periods of brain development has been shown to elicit behavioral features associated with autism diagnosis and has been proposed as a valid animal model of the disorder. The purpose of this study was to characterize sensory and motor performance in rats postnatally treated with valproate. Thirty-four rat pups were injected with either valproate (150 mg/kg) or saline on postnatal days 6-12. Auditory and tactile startle as well as auditory sensory gating was assessed during both the juvenile and adolescent stages of development; motor testing was conducted during late adolescence and included a sunflower seed eating task and a vermicelli handling task. Valproate-treated rats were underresponsive to auditory stimuli, showed deficits in auditory sensory gating, and demonstrated impairments in motor speed and performance. These findings suggest that postnatal valproate treatment elicits sensory and motor features often seen in individuals with ASD. Further, the hyposensitivity seen in postnatally valproate-treated rats contrasted with hypersensitivity previously reported in prenatally valproate-exposed rats. This suggests that timing of teratogenic exposure during early brain development may be important to consider when investigating the neurobiological basis of sensorimotor impairments in ASD.

摘要

虽然自闭症是根据社交缺陷、沟通障碍和重复或刻板行为这三个核心特征来诊断的,但自闭症谱系障碍(ASD)患者中有超过 70%存在其他行为特征,如感官和运动障碍。在大脑发育的敏感时期,向幼鼠暴露于致畸剂丙戊酸已被证明会引起与自闭症诊断相关的行为特征,并被提议作为该疾病的有效动物模型。本研究的目的是描述经丙戊酸钠处理的大鼠的感官和运动表现。34 只幼鼠在出生后第 6-12 天分别接受丙戊酸钠(150mg/kg)或生理盐水注射。在青少年和青少年阶段同时评估听觉和触觉惊跳以及听觉感觉门控;在青少年晚期进行运动测试,包括葵花籽进食任务和粉丝处理任务。丙戊酸钠处理的大鼠对听觉刺激反应迟钝,听觉感觉门控缺陷,运动速度和表现受损。这些发现表明,产后丙戊酸钠处理会引发自闭症患者常见的感官和运动特征。此外,与先前报道的产前丙戊酸钠暴露大鼠的超敏反应相反,产后丙戊酸钠处理的大鼠表现出低敏反应。这表明在研究 ASD 中感觉运动障碍的神经生物学基础时,早期大脑发育期间致畸暴露的时间可能很重要。

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