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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 VPA 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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by several alterations, including disorganized brain cytoarchitecture and excitatory/inhibitory (E/I) imbalance. We aimed to analyze aspects associated with the inhibitory components in ASD, using bioinformatics to develop notions about embryonic life and tissue analysis for postnatal life. We analyzed microarray and RNAseq datasets of embryos from different ASD models, demonstrating that regions involved in neuronal development are affected. We evaluated the effect of prenatal treatment with resveratrol (RSV) on the neuronal organization and quantity of parvalbumin-positive (PV+), somatostatin-positive (SOM+), and calbindin-positive (CB+) GABAergic interneurons, besides the levels of synaptic proteins and GABA receptors in the medial prefrontal cortex (mPFC) and hippocampus (HC) of the ASD model induced by valproic acid (VPA). VPA increased the total number of neurons in the mPFC, while it reduced the number of SOM+ neurons, as well as the proportion of SOM+, PV+, and CB+ neurons (subregion-specific manner), with preventive effects of RSV. In summary, metabolic alterations or gene expression impairments could be induced by VPA, leading to extensive damage in the late developmental stages. By contrast, due to its antioxidant, neuroprotective, and opposite action on histone properties, RSV may avoid damages induced by VPA. [ABSTRACT FROM AUTHOR]