孤独症谱系障碍（ASD）是起始于婴幼儿时期的严重神经发育障碍性疾病，存在明显的多感官异常，其中痛觉异常备受关注，但机制不明。研究表明：背根神经节（DRG）KCNQ钾通道与ASD痛觉异常关系密切；本课题组前期代谢组学研究发现，ASD患儿血清中可调控背根神经节离子通道活性的1-磷酸鞘氨醇（S1P）明显升高，并与其临床表型相关。我们推测，S1P异常可能通过对背根神经节KCNQ钾通道活性的影响而导致ASD痛觉异常形成。本项目以C57BL/6小鼠和BTBR小鼠（ASD模型鼠）为研究对象，通过加入S1P及其受体阻断等方法改变DRG局部环境的S1P水平，应用膜片钳技术、免疫荧光和Western Blot技术，从细胞、分子和器官水平层面，探讨：S1P对DRG神经元KCNQ钾通道活性的作用；S1P经其受体及信号转导通路的介导调控KCNQ钾通道活动的机制。本课题将为ASD患者临床靶向干预提供新思路及理论依据。

Autism Spectrum Disorders (ASD) is a severe neurodevelopmental disorder ,which begins at the stage of infancy and childhood, and they usually show obvious sensory abnormalities ,in which the abnormal pain sensitivity is paid increasing attention ,for which the mechanism is unknown. The current study suggests KCNQ potassium channels in dorsal root ganglion (DRG) neurons might be associated with this disease .Our early metabolism study found that sphingosine 1 phosphate (S1P) level ,which regulates the activity of ion channel in dorsal root ganglion neurons ,increased significantly in serum of children with ASD and correlated with its clinical phenotype .We speculate , the effection of abnormal level of S1P on KCNQ potassium channels in dorsal root ganglion neurons would mediate the formation of abnormal pain sensitivity in ASD. The proposed project will use C57BL/6 and BTBR rats (ASD model mouse) as the research objects, and change the level of S1P through the methods such as giving S1P and the inhibition of its receptor , from cellular 、molecular and organ levels ，by patch clamp、Western Blot and immunity fluorescence technique , to study effection of S1P on KCNQ potassium channels activity and regulatory mechanisms of S1P on KCNQ potassium channels is mediated by its receptors and the relevant signal transduction pathway.To provide the theoretical basis and new idea for clinical targeted intervention for ASD.