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.
Neurosci Bull. 2022 Jul;38(7):753-768. doi: 10.1007/s12264-022-00847-4. Epub 2022 Mar 30.
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.
短暂性脑缺血发作（TIA）可导致认知功能可逆性和延迟性损伤，但具体机制尚不清楚。膜联蛋白 A1（ANXA1）是一种磷脂结合蛋白。在这里，我们证实 TIA 处理的小鼠认知和海马突触受损，而多次轻度刺激（MMS）可挽救这种损伤。TIA 促进了 ANXA1 和 CX3CR1 的相互作用，增加了小胶质细胞中 CX3CR1 的膜分布，从而增强了 CX3CR1 和 CX3CL1 的相互作用。MMS 可逆转 TIA 诱导的这些现象。同时，过表达 ANXA1 的原代培养小胶质细胞中 CX3CR1 的膜分布和 CX3CR1-CX3CL1 相互作用上调，而共培养的过表达 ANXA1 和神经元的小胶质细胞中棘突密度显著降低。此外，小胶质细胞中 ANXA1 的过表达可消除 TIA 后 MMS 的保护作用。综上所述，我们的研究为治疗 TIA 引起的延迟性突触损伤提供了一种潜在策略。
