Plasma exosomal miR-30b-5p attenuates neuroinflammation in a rat model of autism spectrum disorder

Abstract

Background: There is growing evidence that exosomes play an important role in the pathogenesis of central nervous system diseases, but little is known about the relationship between exosomes and autism spectrum disorder (ASD). Methods: In this study, a rat model of ASD was generated via prenatal exposure to valproic acid (VPA). Three-chamber social interaction, self-grooming and marble burying tests were utilized for behavioral assessment. The plasma exosomal microRNA (miRNA) expression profiles of VPA-treated rats and sham rats were analyzed. Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and IL-1β levels were measured by ELISA. miR-30b-5p in the brains was assessed by qRT-PCR. Epidermal growth factor receptor (EGFR), p-p38/p38, and CaMKII were assessed by Western blot. In addition, the regulation of miR-30b-5p/EGFR was examined by lateral ventricle injection with miR-30b-5p agomir in VPA-exposed rats. Results: VPA-exposed rats exhibited ASD-like behaviors. The level of miR-30b-5p was significantly lower in the plasma exosomes and brains of VPA-exposed rats than in those of sham rats. In addition, the levels of inflammatory factors, EGFR, p-p38/p38, and CaMKII were increased in the brains of VPA-exposed rats. Moreover, overexpressing miR-30b-5p ameliorated ASD-like behaviors and decreased the expression of inflammatory factors, EGFR, p-p38/p38, and CaMKII in the brains of VPA-exposed rats. Conclusions: Our study highlights that plasma exosomal miR-30b-5p attenuates neuroinflammation in a rat model of ASD by modulating EGFR through the MAPK signaling pathway and calcium signaling pathway. This study provides novel perspectives on plasma exosomal miR-30b-5p, which could be considered a potential therapeutic target for the treatment of ASD in the clinic.