{"title":"Salidroside Ameliorates Neuroinflammation in Autistic Rats by Inhibiting NLRP3/Caspase-1/GSDMD Signal Pathway.","authors":"Qingwei Wu, Xiaohang Shan, Xuemei Li, Jian Guan, Fanxu Song, Xinyu Zhou, Yingying Fan, Lanmin Guo","doi":"10.1016/j.brainresbull.2024.111132","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Autism spectrum disorder (ASD) is a neurodevelopmental disorder that place a huge economic and emotional burden on society. Salidroside (Sal) has been reported to have therapeutic effects in a variety of neurological disorders such as Alzheimer's disease （AD） and Parkinson's disease (PD), however no studies have been conducted to show whether salidroside is effective in ASD. Pyroptosis is involved in the pathology of a variety of neurological disorders, but has not been reported in ASD.</p><p><strong>Objectives: </strong>The aim of this study was to investigate whether pyroptosis is involved in the pathological mechanisms of ASD, and whether salidroside has an impact on the pathological process of ASD by regulating pyroptosis.</p><p><strong>Methods: </strong>We obtained a rat model of offspring ASD by prenatal intraperitoneal administration of valproic acid (VPA, 500mg/kg) to pregnant rats, and we treated seven-day-old offspring ASD with salidroside (Sal, 30mg/kg once daily) by gavage for 28 days as the salidroside treatment group. We examined the hippocampal state of ASD rats and the effect of salidroside on the hippocampus of VPA-induced ASD rats. In addition, in BV2 cells treated with LPS/Nig, we explored the mechanisms by which salidroside regulates neuroinflammation and pyroptosis in vitro.</p><p><strong>Results: </strong>In vivo, we observed VPA-induced hippocampal neuronal damage and activation of the NLRP3/Caspase-1/GSDMD signalling pathway in ASD rats, while salidroside alleviated neuronal damage in ASD rats. In vitro, we found that salidroside inhibited LPS/Nig-induced neuroinflammation and activation of the NLRP3/Caspase-1/GSDMD signalling pathway. These results suggest that the therapeutic effect of salidroside on hippocampal damage in ASD rats may be related to NLRP3/Caspase-1/GSDMD-mediated pyroptosis.</p><p><strong>Conclusions: </strong>Our work showed that salidroside ameliorates hippocampal neurological damage in ASD rats by targeting NLRP3/Caspase-1/GSDMD-mediated pyroptosis, providing a potential therapy drug for ASD.</p>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":" ","pages":"111132"},"PeriodicalIF":3.5000,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain Research Bulletin","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.brainresbull.2024.111132","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that place a huge economic and emotional burden on society. Salidroside (Sal) has been reported to have therapeutic effects in a variety of neurological disorders such as Alzheimer's disease （AD） and Parkinson's disease (PD), however no studies have been conducted to show whether salidroside is effective in ASD. Pyroptosis is involved in the pathology of a variety of neurological disorders, but has not been reported in ASD.
Objectives: The aim of this study was to investigate whether pyroptosis is involved in the pathological mechanisms of ASD, and whether salidroside has an impact on the pathological process of ASD by regulating pyroptosis.
Methods: We obtained a rat model of offspring ASD by prenatal intraperitoneal administration of valproic acid (VPA, 500mg/kg) to pregnant rats, and we treated seven-day-old offspring ASD with salidroside (Sal, 30mg/kg once daily) by gavage for 28 days as the salidroside treatment group. We examined the hippocampal state of ASD rats and the effect of salidroside on the hippocampus of VPA-induced ASD rats. In addition, in BV2 cells treated with LPS/Nig, we explored the mechanisms by which salidroside regulates neuroinflammation and pyroptosis in vitro.
Results: In vivo, we observed VPA-induced hippocampal neuronal damage and activation of the NLRP3/Caspase-1/GSDMD signalling pathway in ASD rats, while salidroside alleviated neuronal damage in ASD rats. In vitro, we found that salidroside inhibited LPS/Nig-induced neuroinflammation and activation of the NLRP3/Caspase-1/GSDMD signalling pathway. These results suggest that the therapeutic effect of salidroside on hippocampal damage in ASD rats may be related to NLRP3/Caspase-1/GSDMD-mediated pyroptosis.
Conclusions: Our work showed that salidroside ameliorates hippocampal neurological damage in ASD rats by targeting NLRP3/Caspase-1/GSDMD-mediated pyroptosis, providing a potential therapy drug for ASD.
期刊介绍：
The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.
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