Macrophage-Mediated Glial Cell Elimination in the Postnatal Mouse Cochlea.

Macrophage-Mediated Glial Cell Elimination in the Postnatal Mouse Cochlea.
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出生后小鼠耳蜗中巨噬细胞介导的胶质细胞消除。

DOI:
10.3389/fnmol.2017.00407
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发表时间:
2017
影响因子:
4.8
通讯作者:
Lang H
Lang H
中科院分区:
医学2区
文献类型:
--
作者:
Brown LN;Xing Y;Noble KV;Barth JL;Panganiban CH;Smythe NM;Bridges MC;Zhu J;Lang H

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听力依赖于听觉信息通过听觉神经从感觉毛细胞(HC)传输到大脑。这种信息传递需要 HC 以独特的方式受到螺旋神经节神经元 (SGN) 的支配,并且 SGN 被有髓鞘和非髓鞘神经胶质细胞包裹。在发育中的听神经中,错误定位的 SGN 轴突会被缩回或修剪,并且多余的细胞会在称为神经细化的过程中被清除。听觉神经胶质细胞在听觉神经细化过程中是否被消除尚不清楚。使用任一性别的早期产后小鼠,我们发现神经胶质细胞数量在出生后第一周后减少,与发育中的听觉神经的神经细化在时间上相对应。此外,免疫相关基因的表达上调,巨噬细胞数量增加,同时神经胶质细胞数量减少。使用转基因 CD11bDTR/EGFP 小鼠,在早期听神经发育过程中巨噬细胞的瞬时耗竭导致出现过多的神经胶质细胞。巨噬细胞耗竭导致髓磷脂形成异常和血管纹短暂水肿。巨噬细胞耗尽的小鼠还表现出听觉功能受损,但在成年后部分恢复。这些发现表明,巨噬细胞有助于耳蜗出生后发育过程中神经胶质细胞数量的调节,并且神经胶质细胞在听力发生和听神经成熟中发挥着关键作用。
Hearing relies on the transmission of auditory information from sensory hair cells (HCs) to the brain through the auditory nerve. This relay of information requires HCs to be innervated by spiral ganglion neurons (SGNs) in an exclusive manner and SGNs to be ensheathed by myelinating and non-myelinating glial cells. In the developing auditory nerve, mistargeted SGN axons are retracted or pruned and excessive cells are cleared in a process referred to as nerve refinement. Whether auditory glial cells are eliminated during auditory nerve refinement is unknown. Using early postnatal mice of either sex, we show that glial cell numbers decrease after the first postnatal week, corresponding temporally with nerve refinement in the developing auditory nerve. Additionally, expression of immune-related genes was upregulated and macrophage numbers increase in a manner coinciding with the reduction of glial cell numbers. Transient depletion of macrophages during early auditory nerve development, using transgenic CD11bDTR/EGFP mice, resulted in the appearance of excessive glial cells. Macrophage depletion caused abnormalities in myelin formation and transient edema of the stria vascularis. Macrophage-depleted mice also showed auditory function impairment that partially recovered in adulthood. These findings demonstrate that macrophages contribute to the regulation of glial cell number during postnatal development of the cochlea and that glial cells play a critical role in hearing onset and auditory nerve maturation.
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