{"title":"Novel Perspective on Sevoflurane-Induced Cognitive Dysfunction: Implications of Neuronal SIRPα and Microglial Synaptic Remodeling","authors":"Wei Du, Xiaomin Zhang, Songze Li and Xin Xie*, ","doi":"10.1021/acschemneuro.4c0048510.1021/acschemneuro.4c00485","DOIUrl":null,"url":null,"abstract":"<p >This study aims to investigate the role of neuronal SIRPα and microglial synaptic remodeling in sevoflurane-induced cognitive dysfunction in newborn mice. Newborn mice were exposed to sevoflurane, followed by behavioral assessments and single-cell transcriptome sequencing of cortical cells. Lentivirus-mediated overexpression of neuronal SIRPα and assessment of the microglial morphology and synaptic function were conducted. Sevoflurane exposure resulted in social cognitive impairments without affecting motor coordination. Transcriptomic analysis revealed no significant changes in cortical microglial cells or neurons. However, sevoflurane inhibited nonsynaptic synapse modification by microglia. Overexpression of neuronal SIRPα enhanced microglial function, promoted neuron development, and ameliorated cognitive impairments. SCENIC analysis identified a correlation between IRF8 and SIRPα expression. This study sheds light on the involvement of neuronal SIRPα and microglial synaptic remodeling in sevoflurane-induced cognitive dysfunction. Understanding these mechanisms offers new avenues for exploring cognitive impairment pathways and potential therapeutic targets.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"15 24","pages":"4500–4516 4500–4516"},"PeriodicalIF":4.1000,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Chemical Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acschemneuro.4c00485","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
This study aims to investigate the role of neuronal SIRPα and microglial synaptic remodeling in sevoflurane-induced cognitive dysfunction in newborn mice. Newborn mice were exposed to sevoflurane, followed by behavioral assessments and single-cell transcriptome sequencing of cortical cells. Lentivirus-mediated overexpression of neuronal SIRPα and assessment of the microglial morphology and synaptic function were conducted. Sevoflurane exposure resulted in social cognitive impairments without affecting motor coordination. Transcriptomic analysis revealed no significant changes in cortical microglial cells or neurons. However, sevoflurane inhibited nonsynaptic synapse modification by microglia. Overexpression of neuronal SIRPα enhanced microglial function, promoted neuron development, and ameliorated cognitive impairments. SCENIC analysis identified a correlation between IRF8 and SIRPα expression. This study sheds light on the involvement of neuronal SIRPα and microglial synaptic remodeling in sevoflurane-induced cognitive dysfunction. Understanding these mechanisms offers new avenues for exploring cognitive impairment pathways and potential therapeutic targets.
期刊介绍:
ACS Chemical Neuroscience publishes high-quality research articles and reviews that showcase chemical, quantitative biological, biophysical and bioengineering approaches to the understanding of the nervous system and to the development of new treatments for neurological disorders. Research in the journal focuses on aspects of chemical neurobiology and bio-neurochemistry such as the following:
Neurotransmitters and receptors
Neuropharmaceuticals and therapeutics
Neural development—Plasticity, and degeneration
Chemical, physical, and computational methods in neuroscience
Neuronal diseases—basis, detection, and treatment
Mechanism of aging, learning, memory and behavior
Pain and sensory processing
Neurotoxins
Neuroscience-inspired bioengineering
Development of methods in chemical neurobiology
Neuroimaging agents and technologies
Animal models for central nervous system diseases
Behavioral research