谷氨酸-谷氨酰胺循环异常与孤独症谱系障碍研究进展

孤独症谱系障碍（autism spectrum disorder，ASD）是一种多病因神经发育性疾病，人群患病率高，病因复杂多样，包括炎症、自身免疫、基因异常等，但具体发病机制尚不清楚。在哺乳动物中枢神经系统（central nervous system，CNS）中，谷氨酸是最主要的兴奋性神经递质，也是一种潜在的神经毒素，其引起的兴奋毒性可能导致神经细胞的死亡。而星形胶质细胞和神经元之间谷氨酸-谷氨酰胺的代谢偶联，防止了过量的谷氨酸扩散到周围神经元上，进而避免了神经元的过度兴奋，对神经元起到保护作用。有研究表明，谷氨酸-谷氨酰胺循环异常可能为ASD发生的核心机制。因此，对炎症、自身免疫、基因异常等孤独症谱系障碍经典病因与谷氨酸-谷氨酰胺循环之间的联系进行综述，以期为孤独症谱系障碍分型和治疗提供一种新思路。

Progress of Abnormal Glutamate-glutamine Cycle in Autism Spectrum Disorders

Autism spectrum disorder(ASD)is a neurodevelopmental disease with multiple causes,which has a high prevalence rate and complicated causes,including inflammation,autoimmunity,genetic abnormality,etc.,but the specific pathogenesis is still unclear.Glutamate is the most important excitatory neurotransmitter and a potential neurotoxin in the central nervous system(CNS)of mammals,and its excitotoxicity may lead to the death of nerve cells.However,the metabolic coupling of glutamate and glutamine between astrocytes and neurons prevents excessive glutamate from spreading to peripheral neurons,thus avoiding excessive excitation of neurons and protecting neurons.Studies have shown that abnormal glutamate-glutamine cycle may be the core mechanism of ASD.Therefore,the relationship between the classical causes of autism spectrum disorder,such as inflammation,autoimmunity and genetic abnormality,and the glutamate-glutamine cycle was reviewed,in order to provide a new idea for the classification and treatment of autism spectrum disorder.