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.
Tan
Justin
J
The Bionic Ear Institute, 384-388 Albert St, East Melbourne, Victoria 3002, Australia. jtan@bionicear.org
Clarke
Maria
M
Barrett
G
G
Millard
R
R
D000161:Acoustic Stimulation; D000818:Animals; D001309:Auditory Threshold; D016923:Cell Death; D003051:Cochlea / Q000294:innervation*; D003056:Cochlear Nerve / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem; D005838:Genotype; D006317:Hearing Loss, Noise-Induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009622:Noise / Q000009:adverse effects; D010641:Phenotype; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012583:Schwann Cells / Q000378:metabolism; D013045:Species Specificity; D013997:Time Factors; D015854:Up-Regulation
D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse