Triggering Receptor Expressed on Myeloid Cells 2 Alleviated Sevoflurane-Induced Developmental Neurotoxicity via Microglial Pruning of Dendritic Spines in the CA1 Region of the Hippocampus  

作　　者：Li Deng Shao-Yong Song Wei-Ming Zhao Xiao-Wen Meng Hong Liu Qing Zheng Ke Peng Fu-Hai Ji 

机构地区：[1]Department of Anaesthesiology,The First Affiliated Hospital of Soochow University,Suzhou,215006,China [2]Institute of Anaesthesiology,Soochow University,Suzhou,215006,China [3]Department of Anaesthesiology,Dushu Lake Hospital Affiliated of Soochow University,Suzhou,215000,China [4]Department of Anaesthesiology and Pain Medicine,University of California Davis Health,Sacramento,CA,USA [5]Center for Molecular Imaging and Nuclear Medicine,Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education,State Key Laboratory of Radiation Medicine and Protection,School for Radiological and Interdisciplinary Sciences(RAD-X),Suzhou Medical College of Soochow University,Suzhou,215006,China

出　　处：《Neuroscience Bulletin》2024年第9期1215-1229,共15页神经科学通报（英文版）

基　　金：National Natural Science Foundation of China(82072130 and 82001126);Key Medical Research Projects in Jiangsu Province(ZD2022021);Six Talent Peaks Project in Jiangsu Province(WSN-022);Suzhou Clinical Medical Center for Anaesthesiology(Szlcyxzxj202102);Jiangsu Medical Association Anaesthesia Research Project(SYH-32021-0036(2021031));Suzhou Medical Health Science and Technology Innovation Project(SKY2022136);Jiangsu Provincial Colleges of Natural Science General Program(22KJD320002);Health Talent Plan Project in Suzhou(GSWS2022007);Gusu Health Talent Project of Soochow(GSWS2021062).

摘　　要：Sevoflurane induces developmental neurotoxicity in mice;however,the underlying mechanisms remain unclear.Triggering receptor expressed on myeloid cells 2(TREM2)is essential for microglia-mediated synaptic refinement during the early stages of brain development.We explored the effects of TREM2 on dendritic spine pruning during sevoflurane-induced developmental neurotoxicity in mice.Mice were anaesthetized with sevoflurane on postnatal days 6,8,and 10.Behavioral performance was assessed using the open field test and Morris water maze test.Genetic knockdown of TREM2 and overexpression of TREM2 by stereotaxic injection were used for mechanistic experiments.Western blotting,immunofluorescence,electron microscopy,three-dimensional reconstruction,Golgi staining,and whole-cell patch-clamp recordings were performed.Sevoflurane exposures upregulated the protein expression of TREM2,increased microglia-mediated pruning of dendritic spines,and reduced synaptic multiplicity and excitability of CA1 neurons.TREM2 genetic knockdown significantly decreased dendritic spine pruning,and partially aggravated neuronal morphological abnormalities and cognitive impairments in sevoflurane-treated mice.In contrast,TREM2 overexpression enhanced microglia-mediated pruning of dendritic spines and rescued neuronal morphological abnormalities and cognitive dysfunction.TREM2 exerts a protective role against neurocognitive impairments in mice after neonatal exposures to sevoflurane by enhancing microglia-mediated pruning of dendritic spines in CA1 neurons.This provides a potential therapeutic target in the prevention of sevoflurane-induced developmental neurotoxicity.

关 键 词：CA1 neurons Dendritic spines Developmental neurotoxicity MICROGLIA SEVOFLURANE TREM2 

分 类 号：R745[医药卫生—神经病学与精神病学]