Association of the retinol to all-trans retinoic acid pathway with autism spectrum disorder  

作　　者：Yu-Ru Feng Qian Zhang Jing-Kun Miao Ting Yang Jie Chen Hong-Yu Chen Qiu-Hong Mou Xue-Li Xiang Dan Long Qiu-Hong Wei Yuan Wu Ting-Yu Li 

机构地区：[1]Children Nutrition Research Center,Chongqing Key Laboratory of Child Neurodevelopmental and Cognitive Disorders,Ministry of Education Key Laboratory of Child Development and Disorders,National Clinical Research Center for Child Health and Disorders,Children’s Hospital of Chongqing Medical University,No 136,2nd Zhongshan Rd,Yuzhong District,Chongqing,China [2]Department of Pediatrics,Women and Children’Hospital of Chongqing Medical University,Chongqing Health Center for Women and Children,Chongqing,China

出　　处：《World Journal of Pediatrics》2024年第10期1043-1058,共16页世界儿科杂志（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.81771223 to TYL,No.82372559 to JC and No.82304119 to TY);the Chief Medical Expert Studio of Chongqing[No.YWBF(2018)263 to TYL];the China Postdoctoral Science Foundation(No.2023M730448 to TY);the Chongqing Postdoctoral Science Foundation(No.CSTB2023NSCQ-BHX0155).

摘　　要：Background Autism spectrum disorder(ASD)is a complex group of neurodevelopmental disorders.Research has highlighted a close association between the retinoic acid(RA)signaling pathway and ASD.This study investigates alterations in the vitamin A(VA,retinol)to RA metabolic pathway in children with ASD and speculates on the underlying reasons for these changes.We propose a subtype characterized by downregulated RA signaling in ASD,laying the groundwork for precise diagnosis and treatment research.Methods We included 489 children with ASD and 280 typically developing(TD)children.Those with ASD underwent evaluations of core symptoms and neuro-developmental levels,which were conducted by professional developmental behavior physicians using assessment scales.Serum VA and all-trans RA(atRA)levels were determined by high-performance liquid chromatography and ultra-high-performance liquid chromatography–tandem mass spectrometry.The expression levels and concentrations of enzyme molecules such as retinol dehydrogenase 10 were assessed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay.Results Children with ASD exhibited reduced serum atRA,accompanied by a downregulation of atRA synthesis enzymes.The reduction in serum atRA levels was linked not only to VA levels but also to the aberrant expression of metabolic enzymes responsible for atRA.Furthermore,the serum atRA levels in children with ASD were more strongly correlated with core symptoms and neurodevelopmental levels than VA levels.Conclusion Children with ASD exhibited a dual regulation of reduced serum atRA levels,influenced by both VA levels and abnormal expression of atRA metabolic enzymes.

关 键 词：All-trans retinoic acid Autism spectrum disorder Retinoic acid signaling pathway Vitamin A Vitamin A metabolism 

分 类 号：R749.94[医药卫生—神经病学与精神病学]