Autism is a complex heterogeneous neurodevelopmental disorder; previous studies have identified altered immune responses among individuals diagnosed with autism. An imbalance in the production of pro- and anti-inflammatory cytokines and transcription factors plays a role in neurodevelopmental behavioral and autism disorders. BTBR T Itpr3tf/J (BTBR) mice are used as a model for autism， as they exhibit social deficits， communication deficits， and repetitive behaviors compared with C57BL/6J (B6) mice. The adenosine A2A receptor (A2AR) appears to be a potential target for the improvement of behavioral， inflammatory， immune， and neurological disorders. We investigated the effects of the A2AR antagonist S... More
Autism is a complex heterogeneous neurodevelopmental disorder; previous studies have identified altered immune responses among individuals diagnosed with autism. An imbalance in the production of pro- and anti-inflammatory cytokines and transcription factors plays a role in neurodevelopmental behavioral and autism disorders. BTBR T Itpr3tf/J (BTBR) mice are used as a model for autism， as they exhibit social deficits， communication deficits， and repetitive behaviors compared with C57BL/6J (B6) mice. The adenosine A2A receptor (A2AR) appears to be a potential target for the improvement of behavioral， inflammatory， immune， and neurological disorders. We investigated the effects of the A2AR antagonist SCH 5826 (SCH) and agonist CGS 21680 (CGS) on IL-21， IL-22， T-bet， T-box transcription factor (T-bet)， GATA3 (GATA Binding Protein 3)， and CD152 (CTLA-4) expression in BTBR mice. Our results showed that BTBR mice treated with SCH had increased CD4IL-21， CD4IL-22， CD4GATA3， and CD4T-bet and decreased CD4CTLA-4 expression in spleen cells compared with BTBR control mice. Moreover， CGS efficiently decreased CD4IL-21， CD4IL-22， CD4GATA3， and CD4T-bet and increased CD4CTLA-4 production in spleen cells compared with SCH-treated and BTBR control mice. Additionally， SCH treatment significantly increased the mRNA and protein expression levels of IL-21， IL-22， GATA3， and T-bet in brain tissue compared with CGS-treated and BTBR control mice. The augmented levels of IL-21/IL-22 and GATA3/T-bet could be due to altered A2AR signaling. Our results indicate that A2AR agonists may represent a new class of compounds that can be developed for use in the treatment of autistic and neuroimmune dysfunctions.
