A transient ischemic attack(TIA)can cause reversible and delayed impairment of cognition,but the specific mechanisms are still unclear.Annexin al(ANXA1)is a phospholipid-binding protein.Here,we confirmed that cognition and hippocampal synapses were impaired in TIA-treated mice,and this could be rescued by multiple mild stimulations(MMS).TIA promoted the interaction of ANXA1 and CX3CR1,increased the mem-brane distribution of CX3CR1 in microgli\a,and thus enhanced the CX3CR1 and CX3CL1 interaction.These phenomena induced by TIA could be reversed by MMS.Meanwhile,the CX3CR1 membrane distribution and CX3CR1-CX3CL1 interaction were upregulated in primary cultured microglia overexpressing ANXA1,and the spine density was significantly reduced in co-cultured microglia overexpressing ANXA1 and neurons.Moreover,ANXA1 overexpression in microglia abolished the protec-tion of MMS after TIA.Collectively,our study provides a potential strategy for treating the delayed synaptic injury caused by TIA.

Lu Zheng;Yi Wang;Bin Shao;Huijuan Zhou;Xing Li;Cai Zhang;Ning Sun;Jing Shi

Department of Neurobiology,School of Basic Medicine,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Key Laboratory of Neurological Diseases,Ministry of Education,Wuhan 430030,China;The Institute for Brain Research,Collaborative Innovation Center for Brain Science,Huazhong University of Science and Technology,Wuhan 430030,China;Department of Clinical Laboratory,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Department of Immunology,School of Basic Medicine,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

神经科学通报（英文版）

[1]Lu Zheng;Yi Wang;Bin Shao;Huijuan Zhou;Xing Li;Cai Zhang;Ning Sun;Jing Shi-.Multiple Mild Stimulations Reduce Membrane Distribution of CX3CR1 Promoted by Annexin a1 in Microglia to Attenuate Excessive Dendritic Spine Pruning and Cognitive Deficits Caused by a Transient Ischemic Attack in Mice)[J].神经科学通报（英文版）,2022(07):753-768

Stimulations,Attenuate,Deficits,microgli

Multiple,Mild,Reduce,Membrane,Distribution,CX3CR1,Promoted,by,Annexin,a1,Microglia,Excessive,Dendritic,Spine,Pruning,Cognitive,Caused,Transient,Ischemic,Attack,Mice,transient,ischemic,attack,TIA,reversible,delayed,impairment,cognition,specific,mechanisms,are,still,unclear,ANXA1,phospholipid,binding,protein,Here,confirmed,that,hippocampal,synapses,were,impaired,treated,mice,this,could,be,rescued,multiple,mild,stimulations,MMS,promoted,interaction,increased,distribution,thus,enhanced,CX3CL1,These,phenomena,induced,reversed,Meanwhile,membrane,upregulated,primary,cultured,microglia,overexpressing,spine,density,was,significantly,reduced,neurons,Moreover,overexpression,abolished,protec,after,Collectively,our,study,provides,potential,strategy,treating,synaptic,injury,caused

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