ORIGINAL RESEARCH article
Front. Neurosci.
Sec. Neurodevelopment
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1624932
This article is part of the Research TopicNeurodevelopment: parental influences, in utero exposures, and genetics, volume IIView all 4 articles
Oxytocin Enhances Oligodendrocyte Development and Improves Social Deficits in Autistic Rats
Provisionally accepted- 1Guizhou Medical University, Guiyang, China
- 2Qianxinan People's Hospital, XingYi, China
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Purpose: This study aimed to investigate the therapeutic potential of oxytocin and elucidate its underlying molecular mechanisms in a valproic acid (VPA)-induced rat model of autism spectrum disorder (ASD). Methods: An autism rat model was established using chemical intervention during the maternal pregnancy period. The therapeutic effects of oxytocin were evaluated by comparing social behaviors, stereotyped behaviors, and anxiety-like behaviors among the control group, autism model group, and oxytocin-treated group. Furthermore, the amygdala tissues of rats from each group were subjected to transcriptome sequencing. Both threshold and threshold-free bioinformatics analysis methods were employed to identify the potential therapeutic mechanisms of oxytocin. The findings were further validated using transmission electron microscopy and qPCR. Results: Intranasal oxytocin administration significantly ameliorated social deficits, repetitive behaviors, and anxiety-like responses in ASD model rats. Transcriptomic profiling revealed substantial neurodevelopmental abnormalities in VPA-induced ASD model group. Consistent results from GSEA enrichment analysis, dynamic gene expression pattern analysis and WGCNA showed significant suppression of oligodendrocyte development and differentiation in the VPA-induced ASD model group. Pathway analysis indicated that this functional inhibition was associated with the PI3K/AKT signaling pathway. Oxytocin may promote oligodendrocyte development and differentiation by activating the PI3K/AKT pathway, thereby ameliorating social deficits. Further validation by transmission electron microscopy and qPCR confirmed that oxytocin treatment improved myelination deficits in the ASD rat model. Conclusions: Our findings demonstrate that oxytocin significantly improve social interaction deficits in the VPA-induced autism model, which may be related to its activation of the PI3K/AKT pathway to promote oligodendrocyte development and differentiation.
Keywords: Autism Spectrum Disorder, Oxytocin, Amygdala, oligodendrocyte, mitochondrial,
Received: 08 May 2025; Accepted: 21 Jul 2025.
Copyright: © 2025 Min, Zheng, Luo, Zhang and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Bo Zhou, Guizhou Medical University, Guiyang, China
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