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自闭症谱系障碍产前丙戊酸暴露模型中雄性和雌性大鼠发育轨迹的改变。

Altered Developmental Trajectory in Male and Female Rats in a Prenatal Valproic Acid Exposure Model of Autism Spectrum Disorder.

机构信息

Department of Neurophysiology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Main Road, Bengaluru, Karnataka, 560029, India.

Waisman Center, University of Wisconsin-Madison, Madison, 53705, WI, USA.

出版信息

J Autism Dev Disord. 2023 Nov;53(11):4390-4411. doi: 10.1007/s10803-022-05684-y. Epub 2022 Aug 17.

Abstract

Early motor and sensory developmental delays precede Autism Spectrum Disorder (ASD) diagnosis and may serve as early indicators of ASD. The literature on sensorimotor development in animal models is sparse, male centered, and has mixed findings. We characterized early development in a prenatal valproic acid (VPA) model of ASD and found sex-specific developmental delays in VPA rats. We created a developmental composite score combining 15 test readouts, yielding a reliable gestalt measure spanning physical, sensory, and motor development, that effectively discriminated between VPA and control groups. Considering the heterogeneity in ASD phenotype, the developmental composite offers a robust metric that can enable comparison across different animal models of ASD and can serve as an outcome measure for early intervention studies.

摘要

早期运动和感觉发育迟缓先于自闭症谱系障碍 (ASD) 诊断,可能是 ASD 的早期指标。动物模型中关于感觉运动发育的文献很少,以男性为中心,且结果不一。我们对 ASD 的产前丙戊酸 (VPA) 模型中的早期发育进行了表征,发现 VPA 大鼠存在性别特异性发育迟缓。我们创建了一个发育综合评分,结合了 15 项测试结果,提供了一个可靠的整体测量方法,涵盖了身体、感觉和运动发育,能够有效地将 VPA 组和对照组区分开来。考虑到 ASD 表型的异质性,发育综合评分提供了一个强大的指标,可以在不同的 ASD 动物模型之间进行比较,并可作为早期干预研究的结果衡量标准。

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