Oxytocin enhances oligodendrocyte development and improves social deficits in autistic rats
PurposeAutism spectrum disorder (ASD) is a neurodevelopmental condition with complex etiological factors, including genetic predisposition and environmental influences. In particular, exposure to environmental stressors in utero has increasingly been implicated in disrupting fetal neurodevelopment a...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2025.1624932/full |
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| author | Min Wen Min Wen Min Wen Min Wen Shuang Zheng Shuang Zheng Shuang Zheng Hongbo Luo Yi Zhang Yi Zhang Yi Zhang Bo Zhou Bo Zhou Bo Zhou |
| author_facet | Min Wen Min Wen Min Wen Min Wen Shuang Zheng Shuang Zheng Shuang Zheng Hongbo Luo Yi Zhang Yi Zhang Yi Zhang Bo Zhou Bo Zhou Bo Zhou |
| author_sort | Min Wen |
| collection | DOAJ |
| description | PurposeAutism spectrum disorder (ASD) is a neurodevelopmental condition with complex etiological factors, including genetic predisposition and environmental influences. In particular, exposure to environmental stressors in utero has increasingly been implicated in disrupting fetal neurodevelopment and potentially contributing to the pathogenesis of ASD in offspring. The aim of this study was to investigate the therapeutic potential of oxytocin and to elucidate its underlying molecular mechanisms in a valproic acid (VPA) exposure-induced rat model of ASD.MethodsTo generate the ASD offspring model, pregnant rats received intraperitoneal injections of VPA on embryonic day 12.5 (E12.5). A control group was administered saline instead. Only male offspring were included in subsequent experiments. On postnatal day 21 (P21), VPA-exposed offspring were randomly divided into: (1) VPA group (ASD model) and (2) VPA+OT (oxytocin inhaled daily, 400 ug/kg, P21-42) group. Behavioral assessments (social behaviors, stereotyped behaviors, anxiety-like behaviors) and amygdala RNA sequencing were compared across control group, VPA group, and VPA+OT group. 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.ResultsIntranasal oxytocin administration significantly ameliorated social deficits, repetitive behaviors, and anxiety-like responses in ASD model rats. Transcriptomic profiling revealed substantial neurodevelopmental abnormalities in VPA 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 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.ConclusionsOur 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. |
| format | Article |
| id | doaj-art-79440d4925fb438bbbe006ab6bf529cf |
| institution | DOAJ |
| issn | 1662-453X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neuroscience |
| spelling | doaj-art-79440d4925fb438bbbe006ab6bf529cf2025-08-20T03:03:46ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-08-011910.3389/fnins.2025.16249321624932Oxytocin enhances oligodendrocyte development and improves social deficits in autistic ratsMin Wen0Min Wen1Min Wen2Min Wen3Shuang Zheng4Shuang Zheng5Shuang Zheng6Hongbo Luo7Yi Zhang8Yi Zhang9Yi Zhang10Bo Zhou11Bo Zhou12Bo Zhou13State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, Guizhou, ChinaCollege of Pharmacy, Guizhou Medical University, Guiyang, Guizhou, ChinaCollege of Basic Medical, Guizhou Medical University, Guiyang, Guizhou, ChinaGuizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang, Guizhou, ChinaState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, Guizhou, ChinaCollege of Pharmacy, Guizhou Medical University, Guiyang, Guizhou, ChinaGuizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang, Guizhou, ChinaDepartment of Pediatric Healthcare, Qianxinan People's Hospital, Xingyi, Guizhou, ChinaState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, Guizhou, ChinaCollege of Pharmacy, Guizhou Medical University, Guiyang, Guizhou, ChinaGuizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang, Guizhou, ChinaState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, Guizhou, ChinaCollege of Pharmacy, Guizhou Medical University, Guiyang, Guizhou, ChinaGuizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang, Guizhou, ChinaPurposeAutism spectrum disorder (ASD) is a neurodevelopmental condition with complex etiological factors, including genetic predisposition and environmental influences. In particular, exposure to environmental stressors in utero has increasingly been implicated in disrupting fetal neurodevelopment and potentially contributing to the pathogenesis of ASD in offspring. The aim of this study was to investigate the therapeutic potential of oxytocin and to elucidate its underlying molecular mechanisms in a valproic acid (VPA) exposure-induced rat model of ASD.MethodsTo generate the ASD offspring model, pregnant rats received intraperitoneal injections of VPA on embryonic day 12.5 (E12.5). A control group was administered saline instead. Only male offspring were included in subsequent experiments. On postnatal day 21 (P21), VPA-exposed offspring were randomly divided into: (1) VPA group (ASD model) and (2) VPA+OT (oxytocin inhaled daily, 400 ug/kg, P21-42) group. Behavioral assessments (social behaviors, stereotyped behaviors, anxiety-like behaviors) and amygdala RNA sequencing were compared across control group, VPA group, and VPA+OT group. 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.ResultsIntranasal oxytocin administration significantly ameliorated social deficits, repetitive behaviors, and anxiety-like responses in ASD model rats. Transcriptomic profiling revealed substantial neurodevelopmental abnormalities in VPA 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 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.ConclusionsOur 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.https://www.frontiersin.org/articles/10.3389/fnins.2025.1624932/fullautism spectrum disorderoxytocinamygdalaoligodendrocytemitochondrialPI3K/AKT pathway |
| spellingShingle | Min Wen Min Wen Min Wen Min Wen Shuang Zheng Shuang Zheng Shuang Zheng Hongbo Luo Yi Zhang Yi Zhang Yi Zhang Bo Zhou Bo Zhou Bo Zhou Oxytocin enhances oligodendrocyte development and improves social deficits in autistic rats Frontiers in Neuroscience autism spectrum disorder oxytocin amygdala oligodendrocyte mitochondrial PI3K/AKT pathway |
| title | Oxytocin enhances oligodendrocyte development and improves social deficits in autistic rats |
| title_full | Oxytocin enhances oligodendrocyte development and improves social deficits in autistic rats |
| title_fullStr | Oxytocin enhances oligodendrocyte development and improves social deficits in autistic rats |
| title_full_unstemmed | Oxytocin enhances oligodendrocyte development and improves social deficits in autistic rats |
| title_short | Oxytocin enhances oligodendrocyte development and improves social deficits in autistic rats |
| title_sort | oxytocin enhances oligodendrocyte development and improves social deficits in autistic rats |
| topic | autism spectrum disorder oxytocin amygdala oligodendrocyte mitochondrial PI3K/AKT pathway |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2025.1624932/full |
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