Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in both communication and social interaction, besides repetitive or stereotyped behavior. Although the etiology is unknown, environmental factors such as valproic acid (VPA) increase the risk of ASD onset. Resveratrol (RSV), a neuroprotective molecule, has been shown to counteract the effects of intrauterine exposure to VPA. We aimed to evaluate histological parameters related to hippocampal morphology and to the distribution of parvalbumin- (PV), calbindin- (CB), and somatostatin-positive (SOM) interneurons sub-populations, in addition to evaluate the total/phosphorylation levels of PTEN, AKT, GSK3β and total CK2 in the animal model of autism induced by VPA, as well as addressing the potential protective effect of RSV. On postnatal day 120, histological analysis showed a loss in total neurons in the dentate gyrus (DG) and decreased CB+ neurons in DG and CA1 in VPA animals, both prevented by RSV. In addition, PV+ neurons were diminished in CA1, CA2, and CA3, and SOM⁺ were interestingly increased in DG (prevented by RSV) and decreased in CA1 and CA2. A hippocampal lesion similar to sclerosis was also observed in the samples from the VPA group. Besides that, VPA reduced AKT and PTEN immunocontent, and both VPA and RSV increased CK2 immunocontent. Thus, this work demonstrated long-term effects of prenatal exposure to ASD in different sub-populations of interneurons, structural damage of hippocampus, and also alteration in proteins associated with pivotal cell signaling pathways, highlighting the role of RSV as a tool for understanding the pathophysiology of ASD.

自闭症谱系障碍 (ASD) 是一种神经发育障碍，除了重复或刻板行为外，其特征还包括沟通和社交互动障碍。尽管病因尚不清楚，但丙戊酸 (VPA) 等环境因素会增加 ASD 发病的风险。白藜芦醇 (RSV) 是一种神经保护分子，已被证明可以抵消宫内暴露于 VPA 的影响。我们的目的是评估与海马形态以及小白蛋白 (PV)、钙结合蛋白 (CB) 和生长抑素阳性 (SOM) 中间神经元亚群分布相关的组织学参数，此外还评估 PTEN 的总/磷酸化水平、AKT、GSK3β 和总 CK2 在 VPA 诱导的自闭症动物模型中的作用，以及解决 RSV 的潜在保护作用。出生后第 120 天，组织学分析显示 VPA 动物的齿状回 (DG) 神经元总数减少，DG 和 CA1 中 CB+ 神经元减少，这两种情况均被 RSV 阻止。此外，PV+ 神经元在 CA1、CA2 和 CA3 中减少，有趣的是，SOM ⁺在 DG 中增加（被 RSV 阻止），而在 CA1 和 CA2 中减少。在 VPA 组的样本中也观察到类似于硬化的海马病变。除此之外，VPA 降低 AKT 和 PTEN 免疫含量，VPA 和 RSV 均增加 CK2 免疫含量。因此，这项工作证明了产前暴露于 ASD 对不同中间神经元亚群的长期影响、海马的结构损伤以及与关键细胞信号传导途径相关的蛋白质的改变，强调了 RSV 作为理解 ASD 的工具的作用。 ASD 的病理生理学。