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Transforming growth factor β1 inhibition protects from swept-sine violet noise-induced damage

AutorMurillo-Cuesta, Silvia ; Rodriguez-de la Rosa, Lourdes ; Celaya, Adelaida M. ; Camarero, Guadalupe ; Cediel, Rafael ; Sanz, Lorena ; Cobo, Pedro; Rivera, Teresa ; Avendaño, Carlos; Varela-Nieto, Isabel
Fecha de publicación2016
Citación3rd Symposium on Biomedical Research (2016)
ResumenNoise-induced hearing loss (NIHL) is the most common form of acquired deafness and a public health priority in developed countries. Excessive noise damages the principal cochlear structures leading to hearing impairment, inflammatory and immune responses being central mechanisms. Transforming growth factor ß (TGF-ß) is a key regulator of both responses and high levels of this factor have been associated with HL. Refined and reproducible NIHL mice models are essential tools for the evaluation of potential therapeutic drugs. Here we evaluated i) hearing by registering the auditory brainstem response (ABR); ii) cochlear morphology in cresyl-violet stained paraffin sections and iii) protein levels of oxidative stress markers and TGF-ß related genes expression by Western blotting and RT-qPCR, respectively, in mice exposed to a swept-sine-violet (SSV) noise and treated with TGF-ß1 peptidic inhibitors. SSV noise is enriched in frequencies to fit better with the mouse auditory range, two sound levels and frequency range were tested.Results indicate that SSV NIHL mice model is suitable to induce a scalable high frequency cochlear damage depending on the sound level and frequency composition. In addition, we showed that systemic administration of TGF-ß1 inhibitors significantly ameliorate the increase of hearing thresholds, the degenerative cochlear changes and the changes in the inflammatory and redox state induced by noise-exposure. These therapeutic effects were dose-dependent and more effective if the TGF-ß1 inhibitors were administered before noise injury. In conclusion, inhibition of TGF-ß1 actions represents a new, promising therapeutic strategy for the prevention and repair of noise-induced cochlear damage.
DescripciónResumen del póster presentado al 3rd Symposium on Biomedical Research: "Advances and Perspectives in Neuroscience", celebrado en la Universidad Autónoma de Madrid el 22 de abril de 2016.
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