Raghda Elsherif, Amel MM Abdel-Hafez, Ola A. Hussein, Dina Sabry, Lobna A. Abdelzaher, Ayat AH Bayoumy
{"title":"间充质干细胞来源的外泌体对自闭症谱系障碍大鼠小脑组织病理学的潜在改善作用及其对PI3k-mTOR信号传导的调节作用","authors":"Raghda Elsherif, Amel MM Abdel-Hafez, Ola A. Hussein, Dina Sabry, Lobna A. Abdelzaher, Ayat AH Bayoumy","doi":"10.1007/s10735-024-10335-w","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 1","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The potential ameliorative effect of mesenchymal stem cells-derived exosomes on cerebellar histopathology and their modifying role on PI3k-mTOR signaling in rat model of autism spectrum disorder\",\"authors\":\"Raghda Elsherif, Amel MM Abdel-Hafez, Ola A. Hussein, Dina Sabry, Lobna A. Abdelzaher, Ayat AH Bayoumy\",\"doi\":\"10.1007/s10735-024-10335-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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.</p></div>\",\"PeriodicalId\":650,\"journal\":{\"name\":\"Journal of Molecular Histology\",\"volume\":\"56 1\",\"pages\":\"\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-01-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Molecular Histology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s10735-024-10335-w\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Histology","FirstCategoryId":"99","ListUrlMain":"https://link.springer.com/article/10.1007/s10735-024-10335-w","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
The potential ameliorative effect of mesenchymal stem cells-derived exosomes on cerebellar histopathology and their modifying role on PI3k-mTOR signaling in rat model of autism spectrum disorder
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.
期刊介绍:
The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes.
Major research themes of particular interest include:
- Cell-Cell and Cell-Matrix Interactions;
- Connective Tissues;
- Development and Disease;
- Neuroscience.
Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance.
The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.