Mitochondrial Damage and Necroptosis in Aging Cochlea

International Journal of Molecular Sciences

TaeHwan Kim¹  Seong-Hun Jeong²  SungJae Park³  Yang Yu³  MinJung Park³  Ah-Ra Lyu³  Sun-Ae Shin³  Yong-Ho Park³  YangHoon Huh⁴  AReum Je⁴ 

[1] Biomedical Convergence Research Center, Chungnam National University Hospital, Daejeon 35015, Korea;Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea;Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Chungnam National University, Daejeon 35015, Korea;Electron Microscopy Research Center, Korea Basic Science Institute, Cheongju 28119, Korea;

关键词: hearing loss;    age-related;    regional blood flow;    mitochondria;    necroptosis;    cochlea;   

DOI  :  10.3390/ijms21072505

来源: DOAJ

【 摘 要 】

Age-related hearing loss (ARHL) is an irreversible, progressive neurodegenerative disorder and is presently untreatable. Previous studies using animal models have suggested mitochondrial damage and programmed cell death to be involved with ARHL. Thus, we further investigated the pathophysiologic role of mitochondria and necroptosis in aged C57BL/6J male mice. Aged mice (20 months old) exhibited a significant loss of hearing, number of hair cells, neuronal fibers, and synaptic ribbons compared to young mice. Ultrastructural analysis of aged cochleae revealed damaged mitochondria with absent or disorganized cristae. Aged mice also showed significant decrease in cochlear blood flow, and exhibited increase in gene expression of proinflammatory cytokines (IL-1β, IL-6, and TNF-α), receptor-interacting serine/threonine-protein kinase 1 and 3 (RIPK1 and RIPK3) and the pseudokinase mixed-lineage kinase domain-like (MLKL). Immunofluorescence (IF) assays of cytochrome C oxidase I (COX1) confirmed mitochondrial dysfunction in aged cochleae, which correlated with the degree of mitochondrial morphological damage. IF assays also revealed localization and increased expression of RIPK3 in sensorineural tissues that underwent significant necroptosis (inner and outer hair cells and stria vascularis). Together, our data shows that the aging cochlea exhibits damaged mitochondria, enhanced synthesis of proinflammatory cytokines, and provides new evidence of necroptosis in the aging cochlea in in vivo.

【 授权许可】

Unknown