The p75 neurotrophin receptor protects primary auditory neurons against acoustic trauma in mice

In the adult rodent inner ear, p75NTR is weakly expressed in primary auditory neurons (PANs) and cochlear Schwann cells. When the organ of Corti is damaged during trauma, its expression dramatically increases. It is unclear what role p75NTR plays under these conditions. Characterisation of p75NTR mutant mice reveals that altering genetic backgrounds can differentially affect the survival of PANs in mutant mice. To conclusively elucidate the physiological role of p75NTR in the cochlea, we challenged wild type (p75NTR +/+) and mutant (p75NTR −/−) mice with an acoustic trauma at 130 dB SPL, 10 kHz for 2 h. This produces a permanent auditory threshold shift >40 dB SPL, damages the organ of Corti and causes secondary degeneration of PANs. After exposure, mice were maintained for 3-9 weeks. Interestingly, survival of PANs in p75NTR −/− mice was significantly compromised in all time-points when compared to wild type mice: 15% reduction after 3 weeks (n = 6), 32% reduction after 6 weeks (n = 6) and 26% reduction after 9 weeks (n = 6-8). Therefore, our data do not support a role of p75NTR as a death inducer in PANs but show its crucial role in protecting PANs.