Thymol improves autism-like behaviour in VPA-induced ASD rats through the Pin1/p38 MAPK pathway

作者全名："Xiong, Yue; Chen, Jianhui; Lv, Mingqi; Wang, Feifei; Zhang, Hanhong; Tang, Boyi; Li, Yingbo"

作者地址："[Xiong, Yue; Chen, Jianhui; Wang, Feifei; Zhang, Hanhong; Li, Yingbo] Chongqing Med Univ, Inst Neurosci, Cerebrovasc Dis Lab, Chongqing 400016, Peoples R China; [Lv, Mingqi] Chongqing Med Univ, Expt Teaching Management Ctr, Chongqing 400016, Peoples R China; [Tang, Boyi] Chongqing Med Univ, Clin Coll 2, Chongqing 400016, Peoples R China"

通信作者："Li, YB (通讯作者)，Chongqing Med Univ, Inst Neurosci, Cerebrovasc Dis Lab, Chongqing 400016, Peoples R China."

来源：INTERNATIONAL IMMUNOPHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000949720300001

JCR分区：Q1

影响因子：5.6

年份：2023

卷号：117

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Autism spectrum disorders; Valproic acid; Inflammation; Thymol; Pin1; P38 MAPK

摘要："Inflammation plays an essential role in the pathogenesis of autism spectrum disorder (ASD). Thymol is a bioactive monoterpene isolated from Thymus vulgaris that has anti-inflammatory properties and is helpful in neurodevelopmental disorders. The purpose of this study was to investigate the effects of thymol on autism-like behaviours in rats with VPA-induced ASD and to assess the related molecular mechanisms. In the prefrontal cortex (PFC) of the valproic acid (VPA)-exposed rat model, the levels of Pin1, phosphorylated p38 MAPK, interleukin-1 beta (IL-1 beta) and tumour necrosis factor (TNF)-alpha, were increased, and the levels of PSD95 and syn-aptophysin (SYP) decreased. After thymol treatment (30 mg/kg), the VPA-induced autism-like behaviours were alleviated. Moreover, thymol also rescued the dysregulated levels of Pin1, phosphorylated p38 MAPK, IL-1 beta, TNF-alpha, PSD95, and SYP. In addition, immunofluorescence experiments showed that thymol treatment decreased the correlation between Pin1 and phosphorylated p38 MAPK. Mechanistically, Pin1 knockdown by RNA inter-ference confirmed that Pin1 promotes inflammation via phosphorylation of p38 MAPK in the VPA exposure rat model. In conclusion, thymol improved autism-like behaviours in VPA-induced ASD rats by reducing inflam-mation and improving neurodevelopment. This effect was mediated by the Pin1/p38 MAPK pathway. These results experimentally provide the potential for thymol in new therapeutic avenues for autism."

基金机构：Natural Science Foundation of Chongqing [cstc2021jcyj-msxmX0065]

基金资助正文：Acknowledgements This study was supported by the Natural Science Foundation of Chongqing (No. cstc2021jcyj-msxmX0065) .