title: Oxidative stress, inflammation, and autophagic stress as the key mechanisms of premature age-related hearing loss in SAMP8 mouse Cochlea.
abstract: OBJECTIVE
  In our aging society, age-related hearing loss (ARHL) or presbycusis is increasingly important. Here, we study the mechanism of ARHL using the senescence-accelerated mouse prone 8 (SAMP8) which is a useful model to probe the effects of aging on biological processes.
  
  
  RESULTS
  We found that the SAMP8 strain displays premature hearing loss and cochlear degeneration recapitulating the processes observed in human presbycusis (i.e., strial, sensory, and neural degeneration). The molecular mechanisms associated with premature ARHL in SAMP8 mice involve oxidative stress, altered levels of antioxidant enzymes, and decreased activity of Complexes I, II, and IV, which in turn lead to chronic inflammation and triggering of apoptotic cell death pathways. In addition, spiral ganglion neurons (SGNs) also undergo autophagic stress and accumulated lipofuscin.
  
  
  CONCLUSIONS
  Our results provide evidence that targeting oxidative stress, chronic inflammation, or apoptotic pathways may have therapeutic potential. Modulation of autophagy may be another strategy. The fact that autophagic stress and protein aggregation occurred specifically in SGNs also offers promising perspectives for the prevention of neural presbycusis.
authors.affiliation: Institut des Neurosciences de Montpellier, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Menardo
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.forename: Sabine
authors.initials: S
authors.lastname: Ladrech
authors.forename: Marc
authors.initials: M
authors.lastname: Lenoir
authors.forename: François
authors.initials: F
authors.lastname: Casas
authors.forename: Christophe
authors.initials: C
authors.lastname: Michel
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bourien
authors.forename: Jérôme
authors.initials: J
authors.lastname: Ruel
authors.forename: Guy
authors.initials: G
authors.lastname: Rebillard
authors.forename: Tangui
authors.initials: T
authors.lastname: Maurice
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Puel
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
mesh_terms: D000200:Action Potentials; D000367:Age Factors; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D003051:Cochlea / Q000276:immunology / Q000294:innervation / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D042967:Electron Transport Complex I / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D018072:Hair Cells, Auditory, Outer / Q000473:pathology / Q000502:physiology; D007249:Inflammation / Q000378:metabolism*; D008062:Lipofuscin / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D009925:Organ of Corti / Q000378:metabolism / Q000473:pathology; D011304:Presbycusis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013136:Spiral Ganglion / Q000378:metabolism / Q000473:pathology; D013316:Stria Vascularis / Q000473:pathology
chemical_list: D016207:Cytokines; D008062:Lipofuscin; D008315:Malondialdehyde; D042967:Electron Transport Complex I