Melanin precursors prevent premature age-related and noise-induced hearing loss in albino mice

Authors

  • Silvia Murillo-Cuesta,

    1.  Instituto de Investigaciones Biomédicas ‘Alberto Sols’, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), Madrid, Spain
    2.  Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain
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  • Julio Contreras,

    1.  Instituto de Investigaciones Biomédicas ‘Alberto Sols’, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), Madrid, Spain
    2.  Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain
    3.  Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain
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  • Esther Zurita,

    1.  Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain
    2.  Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Department of Molecular and Cellular Biology, Campus de Cantoblanco, Madrid, Spain
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  • Rafael Cediel,

    1.  Instituto de Investigaciones Biomédicas ‘Alberto Sols’, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), Madrid, Spain
    2.  Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain
    3.  Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain
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  • Marta Cantero,

    1.  Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain
    2.  Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Department of Molecular and Cellular Biology, Campus de Cantoblanco, Madrid, Spain
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  • Isabel Varela-Nieto,

    1.  Instituto de Investigaciones Biomédicas ‘Alberto Sols’, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), Madrid, Spain
    2.  Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain
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    • These authors contributed equally to this study.

  • Lluís Montoliu

    1.  Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain
    2.  Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Department of Molecular and Cellular Biology, Campus de Cantoblanco, Madrid, Spain
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    • These authors contributed equally to this study.


Lluís Montoliu, e-mail: montoliu@cnb.csic.es

Summary

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.

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