Poster abstracts
Poster number 61 submitted by Ben Seicol
Chronic inflammation occurs in both the cochlea and the cochlear nucleus during age-related hearing loss
Benjamin J. Seicol (NGP), Shengyin Lin (Department of Otolaryngology, College of Medicine), Ruili Xie (Department of Otolaryngology, College of Medicine)
Abstract:
Age-related hearing loss (ARHL) is an increasingly common age-related pathology characterized by structural changes in the auditory pathway including the cochlea and cochlear nucleus (CN). Cochlear macrophages and CN microglia provide host defense and tissue surveillance. Both are long-lived cell populations that respond to environmental insults to promote and resolve inflammation. Failure to resolve inflammation leads to chronic inflammation that can enhance age-related pathology. While it is known that cellular and tissue damage following acoustic insults are worsened by acute inflammation, the impact of chronic inflammation during ARHL remains unclear. We hypothesized that accumulation and activation of cochlear macrophages and CN microglia occurs during ARHL in mice corresponding with loss of function. To test this, we investigated inflammation in the cochlea and CN of young, middle-aged, and aged CBA/CaJ mice. All mice were tested for auditory brainstem response (ABR) to assess hearing status. Cochlea and cochlear nucleus were collected and immunohistochemistry was used to label tissue with markers targeting ionized calcium binding adaptor molecule 1 (Iba1) and CD68—a marker of phagocytic activity. Confocal microscopy and quantitative image processing were used to measure the accumulation and activation of both cell populations across the lifespan. We found ABR thresholds increase during aging consistent with late-onset ARHL in CBA/CaJ mice. We also observed progressive increases in the area covered by Iba1-labeled macrophages in the osseous spiral lamina (OSL) that correlated with increased ABR threshold during aging. Notably, we found significant accumulation and activation of cochlear macrophages in middle-aged mice, which have relatively normal ABR threshold and prior to overt ARHL. CD68-labeled area increased during aging in both the OSL and CN indicating activation. C1q deposition increased during ARHL in the CN. Our study showed that chronic inflammation occurs in both the cochlea and the CN during aging, even in middle age prior to overt ARHL. These findings suggest that chronic inflammation may precede significant tissue damages of the auditory system and contribute to the development of ARHL.
Keywords: Macrophages, Microglia, Age-related Hearing Loss