The early postnatal activation of A2ARs protects BTBR mice against autism related behavior

Abstract

Abstract Background: Studies mainly focused on the immediate effect of drugs on Autism spectrum disorders (ASD), the complex heterogeneous neurodevelopmental disorders, which been proved involved with the chronic inflammation of the central nervous system. Our studies have explored the positive role of activation of adenosine 2A receptors (A2ARs) in protect adult BTBR mice against autism related behavior from the early postnatal period. However, the exact mechanism underlying the protection of A2ARs has not been comprehensively investigated. Methods: The persistent protection of early postnatal activation of A2ARs in the adult BTBR mice were detected utilizing behavior tests. Pathological variation in the peripheral blood of autism patients were analyzed by transcriptomic analysis, including mroast and protein–protein interactions (PPIs). The clues were further explored and validated by real-time RT PCR, western blotting, immunohistochemistry and transcriptomic analysis in the mouse cortex. The blood brain barrier of mouse were spotted by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Results: Abnormal activation of myeloid cells, especially the neutrophil were detected in the peripheral blood of autism patients and BTBR mouse cortex. The BBB permeability of BTBR mouse were significantly increased, which might facilitated the abnormal infiltration of neutrophils spotted in the BTBR mouse cortex. Further, the early postnatal activation of A2ARs effectively revers the abnormal activation and invading of neutrophils in the mouse cortex, might result in the significantly moderation of the autism related behavior of adult BTBR mice, following decrease of the chronic inflammation in the mouse cortex during the early postnatal period. Conclusions: We found the abnormal condition of myeloid cells in the autism patients and BTBR mice, and the adding infiltration of neutrohpils in the mouse cortex. We concluded that the early activation of A2ARs could effectively decreased the autism related behavior of adult BTBR mice via reversing the abnormal activation of myeloid cells and the pathological invading of neutrophils in the mouse cortex.