<p class="first" id="d2849134e119">Autism is a predominant neurodevelopmental disorder
characterized by impaired communication,
social deficits, and repetitive behaviors. Recent research has proposed that the impairment
of innate immunity may play an important role in autism. Toll-like receptors (TLRs)
are potential therapeutic targets against neuroinflammation. The BTBR T+ Itpr3tf/J
(BTBR) mouse is a well-known model of autism, showing repetitive behaviors such as
cognitive inflexibility and increased grooming as compared to C57BL/6 (B6) mice. Adenosine
A2A receptor (A2AR) signaling is involved in inflammation, brain injury, and lymphocyte
infiltration into the CNS, but the role of A2AR in autism remains unknown. We investigated
the effect of A2AR antagonist SCH 5826 (SCH) and agonist CGS 21680 (CGS) on the expression
levels of TLRs, IL-27, NF-κB p65, and IκBα in BTBR mice. Treatment of BTBR mice with
SCH increased the percentage of splenic CD14+TLR2+ cells, CD14+TLR3+ cells, CD14+TLR4+
cells, and decreased the percentage of CD14+IL-27+ cells, as compared to the untreated
BTBR mice. Our results reveal that BTBR mice treated with CGS had reversal of SCH-induced
immunological responses. Moreover, mRNA and protein expression analyses confirmed
increased expression of TLR2, TLR3, TLR4, and NF-κB p65 in brain tissue, and decreased
IL-27 and IκBα expression following SCH treatment, as compared to the untreated-BTBR
and CGS-treated BTBR mice. Together, these results suggest that the A2AR agonist corrects
neuroimmune dysfunction observed in BTBR mice, and thus has the potential as a therapeutic
approach in autism.
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