Resveratrol regulates Thoc5 to improve maternal immune activation-induced autism-like behaviors in adult mouse offspring

IF 4.8 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xin Zeng , Linlin Fan , Mengyue Li , Qian Qin , Xiuming Pang , Shanyi Shi , Danyang Zheng , Yutong Jiang , Han Wang , Lijie Wu , Shuang Liang
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Abstract

Maternal infection during pregnancy is an important cause of autism spectrum disorder (ASD) in offspring, and inflammatory infiltration caused by maternal immune activation (MIA) can cause neurodevelopmental disorders in the fetus. Medicine food homologous (MFH) refers to a traditional Chinese medicine (TCM) concept, which effectively combines food functions and medicinal effects. However, no previous study has screened, predicted, and validated the potential targets of MFH herbs for treating ASD. Therefore, in this study, we used comprehensive bioinformatics methods to screen and analyze MFH herbs and drug targets on a large scale, and identified resveratrol and Thoc5 as the best small molecular ingredient and drug target, respectively, for the treatment of MIA-induced ASD. Additionally, the results of in vitro experiments revealed that resveratrol increased the expression of Thoc5 and effectively inhibited lipopolysaccharide-induced inflammatory factor production by BV2 cells. Moreover, in vivo, resveratrol increased the expression of Thoc5 and effectively inhibited placental and fetal brain inflammation in MIA pregnancy mice, and improved ASD-like behaviors in offspring.

Abstract Image

白藜芦醇调节 Thoc5,改善成年小鼠后代中由母体免疫激活诱发的自闭症样行为
孕期母体感染是导致后代自闭症谱系障碍(ASD)的重要原因,母体免疫激活(MIA)引起的炎症浸润可导致胎儿神经发育障碍。药食同源(MFH)是指将食物功能与药效有效结合的一种传统中医概念。然而,此前还没有研究对药食同源中药治疗 ASD 的潜在靶点进行筛选、预测和验证。因此,在本研究中,我们采用综合的生物信息学方法对中药材和药物靶点进行了大规模的筛选和分析,发现白藜芦醇和Thoc5分别是治疗MIA诱发的ASD的最佳小分子成分和药物靶点。此外,体外实验结果表明,白藜芦醇能增加Thoc5的表达,有效抑制脂多糖诱导的BV2细胞炎症因子的产生。此外,在体内,白藜芦醇增加了Thoc5的表达,有效抑制了MIA妊娠小鼠的胎盘和胎儿脑部炎症,并改善了后代的ASD样行为。
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来源期刊
Journal of Nutritional Biochemistry
Journal of Nutritional Biochemistry 医学-生化与分子生物学
CiteScore
9.50
自引率
3.60%
发文量
237
审稿时长
68 days
期刊介绍: Devoted to advancements in nutritional sciences, The Journal of Nutritional Biochemistry presents experimental nutrition research as it relates to: biochemistry, molecular biology, toxicology, or physiology. Rigorous reviews by an international editorial board of distinguished scientists ensure publication of the most current and key research being conducted in nutrition at the cellular, animal and human level. In addition to its monthly features of critical reviews and research articles, The Journal of Nutritional Biochemistry also periodically publishes emerging issues, experimental methods, and other types of articles.
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