The Stria Vascularis in Mice and Humans Is an Early Site of Age-Related Cochlear Degeneration, Macrophage Dysfunction, and Inflammation

• DOI: 10.1523/jneurosci.2234-22.2023
• Publication Date: 2023-06-02T17:56:02Z
• Authors: Hainan Lang; Kenyaria V. Noble; Jeremy L. Barth; Jeffrey A. Rumschlag; Tyreek R. Jenkins; Shelby L. Storm; Mark A. Eckert; Judy R. Dubno; Bradley A. Schulte
• Keywords: Pathophysiology

Age-related hearing loss, or presbyacusis, is a common degenerative disorder affecting communication and quality of life for millions older adults. Multiple pathophysiologic manifestations, along with many cellular molecular alterations, have been linked to presbyacusis; however, the initial events causal factors not clearly established. Comparisons transcriptome in lateral wall (LW) other cochlear regions mouse model (of both sexes) “normal” age-related loss revealed that early pathophysiological alterations stria vascularis (SV) are associated increased macrophage activation signature indicative inflammaging, form immune dysfunction. Structure-function correlation analyses mice across lifespan showed age-dependent increase decline auditory sensitivity. High-resolution imaging analysis middle-aged aged human cochleas, transcriptomic changes gene expression, support hypothesis aberrant activity an important contributor strial dysfunction, pathology, loss. Thus, this study highlights SV as primary site degeneration dysregulation system indicators pathology Importantly, novel new methods described here now provide means analyze temporal bones way had previously feasible thereby represent significant tool otopathological evaluation. SIGNIFICANCE STATEMENT neurodegenerative life. Current interventions (primarily aids implants) offer imperfect often unsuccessful therapeutic outcomes. Identification crucial development treatments diagnostic tests. Here, we find SV, nonsensory component cochlea, structural functional humans characterized by cell activity. We also establish technique evaluating cochleas from bones, but understudied area research because lack well-preserved specimens difficult tissue preparation processing approaches.