皮层发育关键期兴奋性/抑制性神经递质和突触失衡致力于自闭症的发生。星形胶质细胞通过谷氨酸转运体GLT1清除谷氨酸在突触间隙堆积，是维持皮层递质平衡的关键因素。腺苷二型受体A2AR下调星形胶质细胞GLT1的表达。我们前期研究发现A2AR拮抗剂能够上调皮层内GLT1，并改善自闭症模型BTBR小鼠的重复行为及社交障碍，提示A2AR可能通过调控GLT-1的转录表达参与自闭症样行为发生，然而调控途径与分子机制仍不清楚。本课题将釆用BTBR小鼠，分析皮层发育关键期A2AR、GLT1表达水平、PI3K/Akt/NF-κB通路活性与皮层内谷氨酸代谢、神经元突触可塑性及自闭症样行为发生及进展程度相关性；采用Luciferase、ChIP、EMSA等技术明确A2AR通过调节Akt磷酸化介导NF-κB对GLT1转录的调节途径与机制。阐明A2AR参与自闭症样行为发生的关键途径与分子机制；为自闭症的防治提供新思路。

Excitatory/inhibitory neurotransmitter and synaptic plasticity imbalance during the critical period of cortex development play important roles of the occurrence of autism. Astrocytes clears up glutamate acuumulation in the synaptic cleft by glutamate transporter GLT1. It is the key to maintain the cortex neurotransmitter balance. Adenosine 2A receptor down-regulate the expression of GLT1 in astrocytes. Our previous studies found A2AR antagonists can raise GLT1 expression in the cortex, accompanied by the improvement of repetitive behavior and social problems of autistic model mice BTBR. These studies suggest A2AR may play an important role in the development of autism by regulating the expression of GLT 1 in transcription level. However, the exact mechanism is still unclear. Our project will adopt BTBR mice, and analysis A2AR, GLT1 expression level, PI3K/Akt/the NF-κB pathway activity, cortex glutamic acid metabolism, neuron synaptic plasticity and autistic like behavior occurrence during the critical period of cortex development. The Luciferase, ChIP, EMSA technologies will take to make sure the exact molecular mechanism of A2AR mediating Akt phosphorylation inducing the regulation of GLT1 transcription by NF-κB, clarifies the key ways of A2AR involved in the development of autism, and provides a new way for prevention and control of autism.