Serum Exosomes Mediate Autism-like Behavior In Mice And Its Mechanism

Autism spectrum disorder(ASD),autism for short,is a group of neurodevelopmental disorders from mild to severe.Patients usually lose social adaptability in early development,which leads to the great defects in language and communication.The global population prevalence has risen in recent years which has been estimated to be over 1 per cent,and the ratio of men over women is about 4:1.Exosome is a kind of vesicle secreted by cells,which mainly plays the role of intercellular communication.After exosome is secreted to the extracellular,it can act on peripheral cells,or act on distal cells to regulate receptor cells through circulation system.Exosome has been considered to be involved in the occurrence or development of neuropsychiatric diseases.However,the mechanism of exosome and whether it can be used as a method of diagnosis or treatment of the disease are still less knew,especially in autism.This study aims to explore the important role of exosome in the pathogenesis of autism,and to provide new ideas and insights for the research and clinical treatment of autism.We established a model of VP A rats before delivery and analyzed the whole genome of hippocampus and prefrontal cortex.The serum exosome taken from rats were injected into mice,exploring the vitally pathogenic and therapeutic role of exosome in autism.Then,transcriptome analysis in the prefrontal cortex of autism-like mice which were caused by exosome was performed,and was combined to analyze with the data of rats.The results are as follows:1.The whole genome analysis of VPA-model rats obtained the differential gene expression profiles in hippocampus and prefrontal cortex.These differentially expressed genes,including those negatively regulated by differentially expressed miRNAs,are enriched in functions related to behaviors,synapses and neurotransmitters.2.Normal mice injected with serum exosomes from model rats were tested for autism-like behavior by three chamber social test,digging behavior test and self-organizing behavior test.Compared with mice injected with healthy exosomes,709 differentially expressed genes were found in prefrontal cortex by transcriptome analysis.Compared with the prefrontal cortex of model rats,these genes are more significantly concentrated in synapses and related genes.3.Model mice injected with serum exosomes of healthy rats through tail vein were tested by three chamber social test,social interaction experiment,digging behavior test and self-organizing behavior test to determine that healthy exosomes can improve their autism-like behaviorThe results showed the whole genome analysis of VPA model rats provides a new insight into the pathogenesis of autism,which is the dysfunction of miRNA and mRNA in the brain may cause autism.In addition,exosomes from VPA model rats can induce autistic behavior in mice,and from healthy rats can significantly improve autistic behavior in VPA model mice,indicating that exosomes play a crucial role in the development and treatment of autism.Moreover,mice with autism-like behavior induced by exosomes have more potential to become a new animal model of autism.Therefore,this study provides a new idea for the pathogenesis of autism,that is,exosomes participate in the occurrence or improvement of autism,and also provides a new animal model of autism for the future.