Oxidative stress in aging in the c57B16/J mouse cochlea.

Presbycusis is a complex of high frequency hearing loss and disproportionat e loss of speech discrimination that is seen concomitantly with physical si gns of aging. Among the most extensively characterized strains of mice that show an early hearing loss is the C57B16/J strain, a strain that shows ear ly onset of high frequency hearing loss at age 6 months and complete hearin g loss by 1 year of age. The histopathology of this strain consists of loss of hair cells and spiral ganglion neurons in the basal turn, with a progre ssion of loss of hair cells and ganglion neurons towards the apical portion of the cochlea as the animal ages. The process of aging has been extensive ly studied and although details differ in various organisms the consensus t oday is that oxidative stress, i.e. free radical-mediated tissue damage, is one of the core mechanisms of aging. Aerobic metabolism results in the cre ation of hydrogen peroxide and reactive oxygen species. These are normally detoxified by a variety of enzymes and free radical scavengers, including s uperoxide dismutase (SOD), catalase and glutathione. To determine whether o xidative stress plays a role in the pathophysiology of hearing loss in this mouse model of presbycusis we determined the relative change in mRNA produ ction for selected free radical detoxifying enzymes in the C57B16/J mouse c ochlea. Using semi-quantitative RT-PCR with tubulin mRNA as a control, rela tive levels of antioxidant enzyme mRNAs were determined. There was an overa ll increase in SOD1 mRNA levels when comparing 1 and 9 month time points, a nd a transient increase in the expression level of catalase mRNA. B6.CAST(Ahl) mice, which carry the C57B16/J genome but receive their AN gene from C AST mice, do not show these alteractions in antioxidant enzyme production. Our results suggest that at an age of 9 months, at which point significant hearing loss has developed, the C57B16/J mouse cochlea is exposed to increa sed levels of free radicals and that the Ahl gene of the C57B16/J mouse med iates this decrease in protective enzymes and therefore increase in levels of oxidative stress.