Melanin precursors prevent premature age-related and noise-induced hearing loss in albino mice.
Strial melanocytes are required for normal development and correct functioning of the cochlea. Hearing deficits have been reported in albino individuals from different species, although melanin appears to be not essential for normal auditory function. We have analyzed the auditory brainstem responses (ABR) of two transgenic mice: YRT2, carrying the entire mouse tyrosinase (Tyr) gene expression-domain and undistinguishable from wild-type pigmented animals; and TyrTH, non-pigmented but ectopically expressing tyrosine hydroxylase (Th) in melanocytes, which generate the precursor metabolite, L-DOPA, but not melanin. We show that young albino mice present a higher prevalence of profound sensorineural deafness and a poorer recovery of auditory thresholds after noise-exposure than transgenic mice. Hearing loss was associated with absence of cochlear melanin or its precursor metabolites and latencies of the central auditory pathway were unaltered. In summary, albino mice show impaired hearing responses during ageing and after noise damage when compared to YRT2 and TyrTH transgenic mice, which do not show the albino-associated ABR alterations. These results demonstrate that melanin precursors, such as L-DOPA, have a protective role in the mammalian cochlea in age-related and noise-induced hearing loss.
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), Madrid, Spain.
Silvia
S
Murillo-Cuesta
Julio
J
Contreras
Esther
E
Zurita
Rafael
R
Cediel
Marta
M
Cantero
Isabel
I
Varela-Nieto
Lluís
L
Montoliu
D000375:Aging / Q000235:genetics / Q000378:metabolism; D019588:Aging, Premature / Q000150:complications / Q000235:genetics; D000417:Albinism / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D016115:Albinism, Oculocutaneous / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006317:Hearing Loss, Noise-Induced / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D006319:Hearing Loss, Sensorineural / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D007980:Levodopa / Q000096:biosynthesis; D008543:Melanins / Q000096:biosynthesis*; D051379:Mice; D008822:Mice, Transgenic; D014442:Monophenol Monooxygenase / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
D008543:Melanins; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D014442:Monophenol Monooxygenase