Autism spectrum disorders (ASD) are neurodevelopmental disorders that are characterized by repetitive behaviors, and impairments in communication and social interaction. Studies have shown that activation of peroxisome proliferator-activated receptor-delta (PPARδ) causes anti-inflammatory effects in animal models of neuroinflammatory diseases. We investigated the possible anti-inflammatory effect of a PPARδ agonist, GW0742 in the BTBR T⁺ Itpr3tf/J (BTBR) mouse model of autism. BTBR and C57BL/6 (B6) mice were treated orally with GW0742 (30 mg/kg, p.o., once daily) for 7 days. Effect of GW0742 treatment on repetitive behavior, marble burying, and thermal sensitivity response was assessed on day 8. We further examined the effect of GW0742 treatment on immunological parameters in splenocytes using flow cytometry (CD4⁺TIM-3⁺, IL-17A⁺TIM-3⁺, IL-17A⁺CD4⁺, RORγT⁺TIM-3⁺, RORγT⁺CD4⁺, Stat3⁺TIM-3⁺, Foxp3⁺TIM-3⁺, Foxp3⁺CD4⁺, and IFN-γ⁺CD4⁺). We also explored the effects of GW0742 on mRNA and protein expression of TIM-3, IL-17A, RORγT, Stat3, IFN-γ, Foxp3, and IL-10 in the brain tissue using RT-PCR and western blot analyses. GW0742 treatment substantially decreased repetitive behaviors, and lowered thermal sensitivity response in BTBR mice. GW0742 attenuated the expression of inflammatory markers such as IL-17A, RORγT, Stat3, TIM-3, and IFN-γ, while upregulating anti-inflammatory markers such as IL-10/Foxp3 both in the brain and periphery of BTBR mice. In conclusion, this study suggests that GW0742 corrects neurobehavioral dysfunction in BTBR mice which is concurrent with modulation of multiple signaling pathways.

自闭症谱系障碍 (ASD) 是神经发育障碍，其特征是重复行为，以及沟通和社交互动障碍。研究表明，过氧化物酶体增殖物激活受体-δ (PPARδ) 的激活在神经炎性疾病的动物模型中引起抗炎作用。^{我们研究了 PPARδ 激动剂 GW0742 在 BTBR T +}中可能的抗炎作用Itpr3tf/J (BTBR) 自闭症小鼠模型。BTBR 和 C57BL/6 (B6) 小鼠用 GW0742 (30 mg/kg, po, 每天一次) 口服治疗 7 天。在第 8 天评估了 GW0742 治疗对重复行为、大理石埋藏和热敏感性反应的影响。我们使用流式细胞术 (CD4 ⁺ TIM-3 ⁺、IL-17A ⁺ TIM ) 进一步检查了 GW0742 治疗对脾细胞免疫学参数的影响-3 ⁺ , IL-17A ⁺ CD4 ⁺ , RORγT ⁺ TIM-3 ⁺ , RORγT ⁺ CD4 ⁺ , Stat3 ⁺ TIM-3 ⁺ , Foxp3 ⁺ TIM-3 ⁺ , Foxp3⁺ CD4 ⁺和 IFN-γ ⁺ CD4 ⁺ )。我们还使用 RT-PCR 和蛋白质印迹分析探讨了 GW0742 对脑组织中 TIM-3、IL-17A、RORγT、Stat3、IFN-γ、Foxp3 和 IL-10 的 mRNA 和蛋白质表达的影响。GW0742 治疗显着降低了 BTBR 小鼠的重复行为，并降低了热敏感性反应。GW0742 减弱了炎症标志物如 IL-17A、RORγT、Stat3、TIM-3 和 IFN-γ 的表达，同时上调了 BTBR 小鼠大脑和外周的抗炎标志物如 IL-10/Foxp3。总之，本研究表明 GW0742 可纠正 BTBR 小鼠的神经行为功能障碍，同时调节多种信号通路。