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 Isc...
Lu Zheng1,2,3 • Yi Wang1,2,3 • Bin Shao1,2,3 • Huijuan Zhou1,2,3 • Xing Li1,2,3 • Cai Zhang4,5 • Ning Sun1,2,3 • Jing Shi1,2,3
1 Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
2 Key Laboratory of Neurological Diseases, Ministry of Education, Wuhan 430030, China
3 The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan 430030, China
4 Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
5 Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Abstract
A transient ischemic attack (TIA) can cause reversible and delayed impairment of cognition, but the specific mechanisms are still unclear. Annexin a1 (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 membrane distribution of CX3CR1 in microglia, 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 protection of MMS after TIA. Collectively, our study provides a potential strategy for treating the delayed synaptic injury caused by TIA.
Keywords
Annexin a1; CX3CR1; Microglia; Dendritic spine pruning; Transient ischemic attack; Multiple mild
stimulations
