The Possible effect of long noncoding RNA cancer susceptibility candidate 2(CASC2)- Derived from Mesenchymal Stem Cells Exosomes- on valproic acid Induced Autism Spectrum Disorder in Rats: Targeting miR-181a/mTOR signaling Pathway | ||
| Egyptian Journal of Histology | ||
| Articles in Press, Accepted Manuscript, Available Online from 03 November 2025 | ||
| Document Type: Original Article | ||
| DOI: 10.21608/ejh.2025.431207.2341 | ||
| Authors | ||
| Fatma Ehab Elmasry* 1; manal mohamed elbatch2; saad eldin abd el fattah abou elnoeman2; Rania Nagi Abd-Elatif3; amira kamel eltokhy2 | ||
| 1biochemistry department,faculty of medicine ,Tanta university,Tanta ,Egypt | ||
| 2biochemistry department,faculty of medicine,tanta university | ||
| 3Biochemistry department, Faculty of Medicine, Tanta University | ||
| Abstract | ||
| Background: Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder that affects a large number of children globally. It is characterized by impairments in social interaction, communication, and repetitive behaviors. Recent advances in molecular biology have highlighted the potential role of long noncoding RNAs (lncRNAs) in modulating neurological disorders. This study aimed to evaluate the therapeutic potential of lncRNA CASC2 delivered via bone marrow-derived mesenchymal stem cell (BM-MSC) exosomes in a rat model of ASD induced by prenatal exposure to valproic acid (VPA). Methods: A total of 45 male Wistar rat pups were randomly assigned to three equal groups: Group I: Healthy control rats. Group II: ASD model rats exposed prenatally to VPA. Group III: ASD rats treated postnatally with BM-MSC-derived exosomes enriched with lncRNA CASC2. Behavioral tests have been carried out at the end of the treatment. Hippocampus was dissected for histopathological analysis. Brain tissue levels of mTOR and AKT were measured by ELISA. Gene expressions of LncRNA CASC2 and miR-181a were assessed by quantitative real-time PCR. Results: Prenatal VPA exposure resulted in repetitive behavior as well as disturbed social behaviors in comparison with control group. Autistic rats illustrated significant rise in mTOR and AKT brain tissue levels in addition to increased miR-181a and decreased LncRNA CASC2 expression levels in comparison with control group, in contrast, treated group illustrated significant reduction in mTOR and AKT brain tissue levels, decreased miR-181a and increased LncRNA CASC2 expression levels compared to autistic rats. Conclusion: The findings indicate that BM-MSC-derived exosomes carrying lncRNA CASC2 may offer a promising therapeutic strategy for ASD. By targeting the mTOR and AKT pathways, these exosomes could potentially alleviate molecular abnormalities associated with ASD, paving the way for future research into RNA-based therapies for neurodevelopmental disorders. | ||
| Keywords | ||
| mTOR; AKT; LncRNA CASC2; Exosomes | ||
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