Elsherif Raghda, Mm Abdel-Hafez Amel, Hussein Ola A, Sabry Dina, Abdelzaher Lobna A, Bayoumy Ayat Ah
Department of Histology, Faculty of Medicine, Assiut University, Assiut, Egypt.
Department of Histology, Sphinx University, Assiut, Egypt.
J Mol Histol. 2025 Jan 6;56(1):65. doi: 10.1007/s10735-024-10335-w.
Autism spectrum disorder (ASD) is a group of severe neurodevelopmental disorders. This study aimed to elucidate the potential ameliorating effect of postnatal administration of MSCs-derived Exo in a rat model of ASD. Male pups were divided into control (Cont), (VPA); pups of pregnant rats injected with VPA subcutaneously (S.C.) at embryonic day (ED) 13, and (VPA + Exo); pups were intravenously (I.V.) injected with MSCs-derived Exo either at postnatal day (P) 21 (adolescent VPA + Exo) or P70 (adult VPA + Exo). They were evaluated for physiological, histopathological and immunohistochemical changes of cerebellar structure, and genetic expression of PI3k and mTOR. The VPA adult group showed increased locomotor activity and impaired social activity, and anxiety. The cerebellar histological structure was disrupted in VPA groups. VPA + Exo groups showed preservation of the normal histological structure of the cerebellum. Immunohistochemical studies revealed enhanced expression of caspase-3, GFAP, Nestin, and VEGF in VPA groups beside modifying PI3K and mTOR genetic expression. MSCs-derived Exo ameliorated most of the rat cerebellar histopathological alterations and behavioral changes. Their mitigating effect could be established through their antiapoptotic, anti-inflammatory and anti-neurogenesis effect besides modifying PI3k-mTOR signaling.
自闭症谱系障碍（ASD）是一组严重的神经发育障碍。本研究旨在阐明产后给予间充质干细胞来源的外泌体（MSCs-derived Exo）对自闭症谱系障碍大鼠模型的潜在改善作用。雄性幼崽被分为对照组（Cont）、丙戊酸组（VPA）；在胚胎第13天（ED13）皮下注射丙戊酸（S.C.）的孕鼠所产幼崽，以及丙戊酸+外泌体组（VPA + Exo）；幼崽在出生后第21天（P21，青少年VPA + Exo）或第70天（P70，成年VPA + Exo）静脉注射（I.V.）间充质干细胞来源的外泌体。对它们进行小脑结构的生理、组织病理学和免疫组织化学变化评估，以及PI3k和mTOR的基因表达评估。丙戊酸成年组表现出运动活动增加、社交活动受损和焦虑。丙戊酸组的小脑组织结构受到破坏。丙戊酸+外泌体组显示小脑正常组织结构得以保留。免疫组织化学研究显示，除了改变PI3K和mTOR基因表达外，丙戊酸组中caspase-3、GFAP、巢蛋白和血管内皮生长因子（VEGF）的表达增强。间充质干细胞来源的外泌体改善了大多数大鼠小脑组织病理学改变和行为变化。它们的缓解作用可以通过其抗凋亡、抗炎和抗神经发生作用以及改变PI3k-mTOR信号通路来实现。
