Iba1-labeled area did not significantly differ between groups, while CD68 increased with age. (H) Summary changes of Iba1- and CD68-labeled area during aging. Dashed square mark AVCN as shown in (A,C,E). Notice, for example, one of two microglia with downregulated P2Y12 (top arrow) also had increased CD68 staining, while the other does not. Importantly, these three approaches to identify activation capture various populations, suggesting heterogeneity of microglial activation in aged mice. Triangles mark: microglia with activation-associated morphology arrows: microglia with major downregulation P2Y12 and stars: microglia with increased CD68 content. (C–F) Same images obtained from middle-aged mice (C,D) and aged mice (E,F). (B) Magnified view of the ROI from (A) scale bar: 25 μm. Dashed line marks the AVCN area for analysis scale bar: 200 μm. (A) Representative images showing the staining of Iba1, CD68, P2Y12, and the overlapped image of Iba1 and CD68 in the AVCN of young mice. 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.Īging cochlea cochlear nucleus complement hearing loss inflammation macrophage microglia.Īge-associated microglia activation in the CN. 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. 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. 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. 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. 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. 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. Age-related hearing loss (ARHL) is a major hearing impairment characterized by pathological changes in both the peripheral and central auditory systems.
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