Expression pattern of oxidative stress-related genes and prestin in the aging fischer 344/NHSD rat cochlea
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Age-related hearing loss (ARHL), presbycusis, is a significant problem for the aging U.S. population. The current study used a Fischer 344/NHsd (F344/NHsd) rat model of ARHL to investigate the effects of age on oxidative stress and antioxidant defense-related genes and prestin in young (2 months old, n=10), middle (12 months old, n=8), and old (21-25 months old, n=10) age groups in relation to auditory function and outer hair cell (OHC) survival. Age-related expression changes in 84 genes were investigated by quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) array (RT 2 ProfilerTM PCR Array, SABiosciences Corp.) using cochlear tissue samples, and prestin expression was investigated by both RT-qPCR and anti-prestin immunolabeling. Auditory function was assessed by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) testing and cochleograms were constructed for OHC examination. F344/NHsd rats showed age-related elevation in ABR thresholds and decreases in DPOAE amplitudes across test frequencies. Only the cochlear middle turn did not show severe OHC loss in the aged animals. The results from RT-qPCR array revealed age-related downregulation in Stearoyl-Coenzyme A desaturase 1 (Scd1) and upregulation in twelve genes: 24-dehydrocholesterol reductase (Dhcr 24), aminoadipate-semialdehyde synthase (Aass), cytoglobin (Cygb), dual oxidase 2 (Duox2), glutathione peroxidase 3 (Gpx3), glutathione peroxidase 6 (Gpx6), glutathione S-transferase, kappa 1 (Gstk1), glutathione reductase (Gsr), NAD(P)H dehydrogenease, quinone 1 (Nqo1), solute carrier family 38, member 5 (Slc38a5), thioredoxin interacting protein (Txnip), and vimentin (Vim), and. Further analysis using linear correlation and regression analyses between gene expression and ABR/DPOAE measurements revealed significant correlations at one or more test frequencies in all 13 genes mentioned above. Upregulation detected in more than half of these significantly-upregulated genes is thought to be caused by the cochlea’s compensatory response to age-related oxidative stress. There was no significant change in prestin gene expression. Prestin immunolabeling showed stronger staining intensity in the old age group, which contradicts the previous study by Chen et al. (2009).