Attenuation of Progressive Hearing Loss in a Model of Age-Related Hearing Loss by a Heat Shock Protein Inducer, Geranylgeranylacetone

Brain Res. 2008 May 30;1212:9-17. doi: 10.1016/j.brainres.2008.03.031. Epub 2008 Mar 28.

Abstract

Mechanisms of age-related hearing loss (ARHL) have not been elucidated as aging processes are extremely complex. Although oxidative stress and apoptotic cell death are involved in progression of ARHL, number of trial to treat ARHL is limited. Heat shock response is characterized by induction of heat shock proteins (HSPs) in response to stresses such as heat shock, which diminishes during aging. HSPs act as molecular chaperones, and some HSPs also inhibit apoptotic pathways. Here, we examined age-related expression of HSPs in the cochlea of ARHL model DBA/2J mice and control CBA/N mice. Western blot assay revealed that CBA/N mice showed constant expression of Hsp70 and Hsp110 with age, but not in DBA/2J mice. The result suggests that pharmacological upregulation of HSPs might attenuate ARHL. We administered DBA/2J mice with food containing geranylgeranylacetone (GGA) that induces HSPs in the cochlea, and found that its administration suppresses ARHL examined by ABR test and histological examination though protection is specific for the apical part of the cochlea. These results demonstrate that dietary supplementation of GGA could be an effective therapeutic strategy for treatment of ARHL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Animals
  • Anti-Ulcer Agents / administration & dosage*
  • Brain / metabolism
  • Cell Count
  • Cochlea / metabolism
  • Cochlea / pathology
  • Disease Models, Animal
  • Diterpenes / administration & dosage*
  • Dose-Response Relationship, Drug
  • Evoked Potentials, Auditory, Brain Stem / drug effects
  • Gene Expression Regulation / drug effects
  • HSP110 Heat-Shock Proteins / metabolism
  • HSP70 Heat-Shock Proteins / metabolism
  • Hair Cells, Auditory / pathology
  • Male
  • Mice
  • Mice, Inbred DBA
  • Presbycusis / drug therapy*
  • Presbycusis / pathology
  • Presbycusis / physiopathology
  • Psychophysics

Substances

  • Anti-Ulcer Agents
  • Diterpenes
  • HSP110 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • geranylgeranylacetone