Yu Chaorong, Gao Hui-Ming, Wan Guoqiang
MOE Key Laboratory of Model Animal for Disease Study, Department of Otorhinolaryngology-Head and Neck Surgery, The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing, China.
Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, China.
Front Cell Neurosci. 2021 Oct 21;15:736120. doi: 10.3389/fncel.2021.736120. eCollection 2021.
Ribbon synapses of cochlear hair cells undergo pruning and maturation before the hearing onset. In the central nervous system (CNS), synaptic pruning was mediated by microglia, the brain-resident macrophages, activation of the complement system. Whether a similar mechanism regulates ribbon synapse pruning is currently unknown. In this study, we report that the densities of cochlear macrophages surrounding hair cells were highest at around P8, corresponding well to the completion of ribbon synaptic pruning by P8-P9. Surprisingly, using multiple genetic mouse models, we found that postnatal pruning of the ribbon synapses and auditory functions were unaffected by the knockout of the complement receptor 3 (CR3) or by ablations of macrophages expressing either LysM or Cx3cr1. Our results suggest that unlike microglia in the CNS, macrophages in the cochlea do not mediate pruning of the cochlear ribbon synapses.
耳蜗毛细胞的带状突触在听力开始前会经历修剪和成熟过程。在中枢神经系统(CNS)中,突触修剪是由小胶质细胞(即驻留在大脑中的巨噬细胞)介导的,通过补体系统的激活来实现。目前尚不清楚是否有类似机制调节带状突触的修剪。在本研究中,我们报告称,围绕毛细胞的耳蜗巨噬细胞密度在出生后第8天左右最高,这与出生后第8至9天带状突触修剪的完成情况高度吻合。令人惊讶的是,使用多种基因小鼠模型,我们发现带状突触的出生后修剪和听觉功能不受补体受体3(CR3)敲除或表达LysM或Cx3cr1的巨噬细胞消融的影响。我们的结果表明,与中枢神经系统中的小胶质细胞不同,耳蜗中的巨噬细胞不介导耳蜗带状突触的修剪。