孤独症谱系障碍（ASD）是一种病因不明的神经发育障碍性疾病。已证实ASD与神经突触传导异常有关。本课题组发现PUFAs代谢异常与ASD发病有一定关联，但机制不明。内源性大麻素（eCB）样物质由神经元细胞膜中的PUFAs分解而来，作用于突触前膜相关受体，进而抑制突触前神经元神经递质释放，影响突触可塑性形成，推测eCB系统可能与ASD的认知及社交功能密切相关。本项目以ASD儿童和VPA大鼠为研究对象，进行体内eCB样物质水平及eCB系统相关受体、代谢酶表达的病例-对照研究；观察大麻二酚干预后VPA大鼠eCB系统表达的变化及认知和社交功能改变，探讨eCB系统与ASD认知及社交功能的关联。采用膜片钳技术，以与突触可塑性密切相关PI3K-Akt/Ras-ERK-mTOR双信号转导通路为靶点，观察eCB系统对神经元突触可塑性的影响和调控作用，揭示eCB系统对ASD认知及社交功能的影响及可能的作用机制。

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with unclear causes. It has been identified that the synaptic neurotransmission dysfunction was correlated to ASD. Our previous work has reported that the association between abnormal polyunsaturated fatty acid (PUFA) metabolism and the occurrence of ASD, however, the underlying mechanism was still unknown. Endocannabinoids are produced “on demand” from PUFAs present in phospholipids in the neuronal cell membranes, binding with their type-1 and type-2 cannabinoid receptors in the presynaptic neuron, and then inhibit the release of several neurotransmitters and affect synaptic plasticity. We hypothesized that there is potential relationship between endocannabinoid system and cognitive and social impairments in autistic children. In the current study, the autistic children and valproic acid (VPA)–induced rat autism model are used as the research objects to analyze the levels of endocannabinoids, cannabinoid receptors and related key enzymes by case control method, and to observe the change of cognitive and social function and the change of endocannabinoid system’s expressions after cannabidiol intervention, in order to explore the connection between endocannabinoid system and cognitive and social impairments. Furthermore, we also use path clamp technique to detect the effect of endocannabinoid system on neuronal synaptic plasticity based on PI3K-Akt/Ras-ERK-mTOR signal transduction pathways, to explore the potential mechanism that endocannabinoid system play an important role in regulating cognitive and social function.