Background Previous studies have mainly focused on the immediate effect of drugs on autism spectrum disorders (ASDs) and complex heterogeneous neurodevelopmental disorders that have been proven to be involved with the chronic inflammation of the central nervous system. Our prior work has explored the positive role of activation of adenosine 2A receptors (A2ARs) in protecting adult BTBR T+ Itpr3tf/J mice against autism-related behaviour 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 adult BTBR mice was detected utilizing behaviour tests. Pathological variation in the peripheral blood of autism patients was analysed by transcriptomic analysis, including MROAST and protein–protein interaction (PPI) analysis. 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 mice was identified by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Results Abnormal activation of myeloid cells, especially neutrophils, was detected in the peripheral blood of autism patients and the BTBR mouse cortex. The BBB permeability of BTBR mice was significantly increased, which may have facilitated the abnormal infiltration of neutrophils observed in the BTBR mouse cortex. Furthermore, the early postnatal activation of A2ARs effectively reverses the abnormal activation and invasion of neutrophils in the mouse cortex and might result in the significant moderation of autism-related behaviour in adult BTBR mice, followed by a decrease in chronic inflammation in the mouse cortex during the early postnatal period. Conclusions We found abnormal myeloid cells in autism patients and BTBR mice and increased infiltration of neutrophils in the mouse cortex. We concluded that the early activation of A2ARs could effectively decrease the autism-related behaviour of adult BTBR mice by reversing the abnormal activation of myeloid cells and the pathological invasion of neutrophils in the mouse cortex.

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.