Maternal LPS Exposure Enhances the 5-HT Level in the Prefrontal Cortex of Autism-like Young Offspring

作者全名："Lin, Fang; Wang, Xinyuan; Luo, Ruifang; Yuan, Binlin; Ye, Shasha; Yang, Ting; Xiao, Lu; Chen, Jie"

作者地址："[Lin, Fang; Wang, Xinyuan; Luo, Ruifang; Yuan, Binlin; Ye, Shasha; Yang, Ting; Xiao, Lu; Chen, Jie] Chongqing Med Univ, Childrens Nutr Res Ctr, Chongqing Key Lab Childhood Nutr & Hlth, Childrens Hosp, Chongqing 400015, Peoples R China; [Lin, Fang; Wang, Xinyuan; Luo, Ruifang; Yuan, Binlin; Ye, Shasha; Yang, Ting; Xiao, Lu; Chen, Jie] Minist Educ, Natl Clin Res Ctr Child Hlth & Disorders, Key Lab Child Dev & Disorders, Chongqing 400015, Peoples R China; [Xiao, Lu] Chongqing Med Univ, Childrens Hosp, Dept Gastroenterol, Chongqing 400015, Peoples R China"

通信作者："Chen, J (通讯作者)，Chongqing Med Univ, Childrens Nutr Res Ctr, Chongqing Key Lab Childhood Nutr & Hlth, Childrens Hosp, Chongqing 400015, Peoples R China.; Chen, J (通讯作者)，Minist Educ, Natl Clin Res Ctr Child Hlth & Disorders, Key Lab Child Dev & Disorders, Chongqing 400015, Peoples R China."

来源：BRAIN SCIENCES

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001014262500001

JCR分区：Q3

影响因子：2.7

年份：2023

卷号：13

期号：6

开始页：　

结束页：　

文献类型：Article

关键词：serotonin (5-HT); tryptophan metabolism; medial prefrontal cortex (mPFC); autism spectrum disorder (ASD); lipopolysaccharide (LPS)

摘要："Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by reduced social interactions, impaired communication, and stereotyped behavior. The aim of this research is to investigate the changes in serotonin (5-HT) in the medial prefrontal cortex (PFC) of autism-like offspring induced by maternal lipopolysaccharide (LPS) exposure. Pregnant Sprague-Dawley rats were intraperitoneally injected with LPS to establish an autism-like model in their offspring. Offspring prenatally exposed to LPS showed autism-like behavior. The serotonin level in the mPFC of 2-week-old offspring was noticeably increased after maternal LPS exposure. Differentially expressed genes (DEGs) were enriched in pathways related to tryptophan metabolism and the serotonin system, as shown in RNA-seq findings. Consistently, tryptophan and serotonin metabolisms were altered in 2-week-old LPS-exposed offspring. The mRNA expression levels of 5-HT catabolic enzymes were remarkably reduced or tended to decrease. Moreover, maternal LPS exposure resulted in a higher serotonin 1B receptor (5-HT1BR) expression level in the mPFC but no difference in tryptophan hydroxylase 2 (TPH2) or serotonin reuptake transporter (SERT). The concentrations of 5-HT in serum and colon were increased in LPS-exposed offspring. Meanwhile, the expression level of tryptophan hydroxylase 1 (TPH1) in the colon was increased after maternal LPS treatment, whereas SERT was reduced. Furthermore, Golgi-Cox staining showed that neuronal dendritic length and spine density were significantly reduced in the mPFC of LPS-exposed offspring. The current study reveals that maternal LPS treatment resulted in an exaltation of the 5-HT of mPFC in ASD-like young rats, which may partly be caused by the abnormal elevation of 5-HT metabolism in its colon."

基金机构：National Nature Science of Foundation of China [81770526]; Postdoctoral Science Foundation of Chongqing Natural Science Foundation [CSTB2022NSCQ-BHX0664]

基金资助正文：This work was supported by grants from the National Nature Science of Foundation of China (No. 81770526) and the Postdoctoral Science Foundation of Chongqing Natural Science Foundation (No. CSTB2022NSCQ-BHX0664).