Age-related hearing loss in TrpV1 knockout mice

Abstract

Several transient receptor potential (TRP) channels including TRPV1 are located on hair cell membranes. The gating mechanisms of these channels are associated with cellular stress, inflammation, and cytoplasmic uptake of aminoglycosides. Thus, TRPV1 channel may serve as a functional target that links acoustic trauma and enhanced aminoglycoside trafficking. TrpV1 mutant mice have no apparent hearing loss as young adults. Here, we assessed the hearing sensitivity of TrpV1 mutant mice (B6.129X1-Trpv1tm1Jul/J, stock #3770) by auditory brainstem responses to a broad frequency range, from 4 to 48 kHz. At 7 weeks of age, the auditory sensitivity in TrpV1 mutant mice was comparable to their heterozygous littermates. By 11 weeks of age, mutant TrpV1 mice exhibited evident high frequency hearing loss, with 30-to-40 dB elevated thresholds between 24 and 48 kHz, compared to littermate controls. At 18 weeks of age, high frequency hearing sensitivity worsened in both groups of mice, and this age-related progressive hearing loss was further expedited in TrpV1 mutant mice compared to littermate controls. Further research is required to determine the otoprotective role of TRPV1 channel in maintaining auditory sensitivity as mice age, and whether TrpV1 functionality exacerbates aminoglycoside-induced ototoxicity.