Pettie Michaela A, Wilkin-Krug Linda C M, Ellenbroek Bart
Department of Pathology and Biomedical Science, Ōtākou Whakaihu Waka - University of Otago, Christchurch, New Zealand.
Department of Psychology, Julius-Maximilians-University Würzburg, Würzburg, Germany.
Curr Top Behav Neurosci. 2025;75:43-68. doi: 10.1007/7854_2025_603.
This review investigates the teratogenic impact of valproic acid (VPA) on brain development, focusing on dose-dependent and timing-related behavioural and neurological outcomes in rats and mice, with an emphasis on using it as a model for autism spectrum disorders (ASD). Single and multiple administration methods (e.g., oral gavage and intraperitoneal injections) across various rat and mouse strains consistently report behavioural alterations (i.e., altered social interaction and locomotor activity) and neuronal changes, particularly in the hippocampus and cerebellum. We underscore the importance of understanding dose-related changes and the critical role of VPA exposure in determining the long-term neurodevelopmental effects. While animal models provide valuable insights into the pre- and postnatal effects of drug exposure, this chapter also addresses the limitation of extrapolating such findings to humans given the face and construct validity of the model. Overall, this review emphasises VPA's utility in modelling ASD-like behaviours and the need for ongoing research to refine these models for better applicability to humans.
本综述研究了丙戊酸（VPA）对大脑发育的致畸影响，重点关注大鼠和小鼠中与剂量和时间相关的行为及神经学结果，尤其强调将其用作自闭症谱系障碍（ASD）的模型。在各种大鼠和小鼠品系中采用单次和多次给药方法（如灌胃和腹腔注射），均一致报告了行为改变（即社交互动和运动活动改变）以及神经元变化，特别是在海马体和小脑中。我们强调了解剂量相关变化的重要性以及VPA暴露在确定长期神经发育影响方面的关键作用。虽然动物模型为药物暴露的产前和产后影响提供了有价值的见解，但鉴于该模型的表面效度和结构效度，本章也讨论了将此类研究结果外推至人类的局限性。总体而言，本综述强调了VPA在模拟ASD样行为方面的效用，以及持续开展研究以完善这些模型从而更好地应用于人类的必要性。
