Age-Related Hearing Loss Is Accompanied by Chronic Inflammation in the Cochlea and the Cochlear Nucleus.
Age-Related Hearing Loss Is Accompanied by Chronic Inflammation in the Cochlea and the Cochlear Nucleus.
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DOI：
10.3389/fnagi.2022.846804
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发表时间：
2022
影响因子：
4.8
通讯作者：
Xie R
中科院分区：
文献类型：
--
作者：
Seicol BJ;Lin S;Xie R
听觉相关性听力损失（ARHL）是一种以外周和中枢听觉系统病变为特征的主要听力损害。在患有ARHL的死亡人类受试者和早发性ARHL动物模型的耳蜗中观察到低度炎症，这表明炎症有助于ARHL的发展。然而，在耳蜗的正常老化过程中，慢性炎症是如何发展的，特别是中枢听觉系统中神经炎症的伴随变化，仍然是难以捉摸的。为了解决这个问题，我们研究了CBA/CaJ小鼠耳蜗和耳蜗核（CN）的慢性炎症，CBA/CaJ小鼠是一种近交系小鼠，经历正常衰老并发展为人类，如迟发型ARHL。使用免疫组织化学，共聚焦显微镜，和定量图像处理，我们测量的积累和激活的巨噬细胞在耳蜗和小胶质细胞在CN使用其共享的标志物：离子钙结合适配器分子1（Iba 1）和CD 68-吞噬活性的标志物。我们发现逐渐增加的Iba 1标记的巨噬细胞覆盖的区域和增强的CD 68染色的骨螺旋板的耳蜗，在整个寿命与ABR阈值升高。在此过程中，我们进一步确定了CN中小胶质细胞活化和C1 q沉积的显著增加，表明中枢听觉系统中神经炎症和补体活化增加。我们的研究表明，在正常老化过程中，慢性炎症发生在外周和中枢听觉系统，这可能有助于协调发展的ARHL。
Age-related hearing loss (ARHL) is a major hearing impairment characterized by pathological changes in both the peripheral and central auditory systems. Low-grade inflammation was observed in the cochlea of deceased human subjects with ARHL and animal models of early onset ARHL, which suggests that inflammation contributes to the development of ARHL. However, it remains elusive how chronic inflammation progresses during normal aging in the cochlea, and especially the accompanying changes of neuroinflammation in the central auditory system. To address this, we investigated chronic inflammation in both the cochlea and the cochlear nucleus (CN) of CBA/CaJ mice, an inbred mouse strain that undergoes normal aging and develops human, like-late-onset ARHL. Using immunohistochemistry, confocal microscopy, and quantitative image processing, we measured the accumulation and activation of macrophages in the cochlea and microglia in the CN using their shared markers: ionized calcium binding adaptor molecule 1 (Iba1) and CD68—a marker of phagocytic activity. We found progressive increases in the area covered by Iba1-labeled macrophages and enhanced CD68 staining in the osseous spiral lamina of the cochlea that correlated with elevated ABR threshold across the lifespan. During the process, we further identified significant increases in microglial activation and C1q deposition in the CN, indicating increased neuroinflammation and complement activation in the central auditory system. Our study suggests that during normal aging, chronic inflammation occurs in both the peripheral and the central auditory system, which may contribute in coordination to the development of ARHL.
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影响因子：
5.3
作者：
Kalinec GM;Lomberk G;Urrutia RA;Kalinec F
通讯作者：
Kalinec F
出生后小鼠耳蜗中巨噬细胞介导的胶质细胞消除。
影响因子：
4.8
作者：
Brown LN;Xing Y;Noble KV;Barth JL;Panganiban CH;Smythe NM;Bridges MC;Zhu J;Lang H
通讯作者：
Lang H
影响因子：
7.3
作者：
Liu W;Molnar M;Garnham C;Benav H;Rask-Andersen H
通讯作者：
Rask-Andersen H
柯蒂氏器常驻细胞中耳蜗免疫的分子特征。
影响因子：
9.3
作者：
Cai Q;Vethanayagam RR;Yang S;Bard J;Jamison J;Cartwright D;Dong Y;Hu BH
通讯作者：
Hu BH
影响因子：
3.3
作者：
Lin, Shengyin;Xie, Ruili
通讯作者：
Xie, Ruili