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Sensory and Motor Characterization in the Post-natal Valproate Rat Model of Autism

机译:孤独症产后丙戊酸盐大鼠模型的感觉和运动表征

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摘要

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. 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 post-natally treated with valproate. Thirty four rat pups were injected with either valproate (150 mg/kg) or saline on post-natal 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 under-responsive to auditory stimuli, showed deficits in auditory sensory gating, and demonstrated impairments in motor speed and performance. These findings suggest that post-natal valproate treatment elicits sensory and motor features often seen in individuals with ASD. Further, the hypo-sensitivity seen in post-natally valproate-treated rats contrasted with hyper-sensitivity previously reported in pre-natally 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 sensory-motor impairments in ASD.
机译:尽管自闭症是根据社交缺陷,沟通障碍以及重复或刻板行为的三个核心特征进行诊断的,但自闭症谱系障碍患者中仍有70%以上存在其他行为特征,例如感觉障碍和运动障碍。研究表明,在大脑发育的敏感时期,将幼鼠暴露于丙戊酸致畸菌会引起与自闭症诊断有关的行为特征,并被提议作为该疾病的有效动物模型。这项研究的目的是表征在用丙戊酸治疗后的大鼠的感觉和运动表现。在出生后6至12天,向34只大鼠幼鼠注射丙戊酸盐(150 mg / kg)或生理盐水。在发育的青少年阶段评估听觉和触觉惊吓以及听觉感觉门控。运动测试是在青春期后期进行的,其中包括食用葵花籽的任务和处理细面条的任务。用丙戊酸盐治疗的大鼠对听觉刺激反应不足,显示出听觉感觉门控不足,并表现出运动速度和性能受损。这些发现表明,产后丙戊酸盐治疗会引起通常在ASD患者中出现的感觉和运动功能。此外,在出生后接受丙戊酸盐治疗的大鼠中看到的低敏感性与先前在出生前接受丙戊酸盐暴露的大鼠中报道的高敏感性形成对比。这表明在调查ASD感觉运动障碍的神经生物学基础时,在早期大脑发育过程中接触致畸物的时间可能很重要。

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