摘要
小胶质细胞是调节大脑突触发育和可塑性的重要细胞类型,但其影响突触的正常功能的机制尚不清楚。在本研究中,我们通过PLX5622造成小胶质细胞耗竭,并观察其对成年野生型小鼠海马CA3-CA1突触的影响。在小胶质细胞耗竭后,与树突棘密度降低相关的自发和诱发谷氨酸能活动的减少,出现未成熟突触特征以及突触的可塑性提高。小胶质细胞耗竭的小鼠在新物体识别任务的获取方面表现出缺陷。海马星形胶质细胞出现增生,但并没有神经炎症反应。在Cx3cr1-/-小鼠中,PLX不能导致海马出现上述改变。这说明CX3CL1/CX3CR1轴在小胶质细胞对突触功能的控制中有重要作用。PLX5622停用后,小胶质细胞的重新增殖,海马突触恢复,小鼠的学习功能也出现恢复。综上所述,小胶质细胞对维持成人大脑的突触的正常功能用重要的作用,去除小胶质细胞会导致谷氨酸能突触组织和活动的可逆变化。
Microglia cells are active players in regulating synaptic development and plasticity in the brain.However,how they influence the normal functioning of synapses is largely unknown.In this study,we characterized the effects of pharmacological microglia depletion,achieved by administration of PLX5622,on hippocampal CA3-CA1 synapses of adult wild type mice.Following microglial depletion,we observed a reduction of spontaneous and evoked glutama-tergic activity associated with a decrease of dendritic spine density.We also observed the appearance of immature syn-aptic features and higher levels of plasticity.Microglia depleted mice showed a deficit in the acquisition of the Novel Object Recognition task.These events were accompanied by hippocampal astrogliosis,although in the absence of neu-roinflammatory condition.PLX-induced synaptic changes were absent in Cx3cr1-/-mice,highlighting the role of CX3CL1/CX3CR1 axis in microglia control of synaptic functioning.Remarkably,microglia repopulation after PLX5622 withdrawal was associated with the recovery of hippocampal synapses and learning functions.Altogether,these data demonstrate that microglia contribute to normal synaptic functioning in the adult brain and that their remov-al induces reversible changes in organization and activity of glutamatergic synapses.
出处
《神经损伤与功能重建》
2021年第10期F0003-F0003,共1页
Neural Injury and Functional Reconstruction
