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IGF-1 deficit predisposes to noise-induced hearing loss in mice

AuthorsCelaya, Adelaida M. ; Murillo-Cuesta, Silvia ; Rodriguez-de la Rosa, Lourdes ; Cediel, Rafael ; Contreras, Julio ; Avendaño, Carlos; Varela-Nieto, Isabel
Issue Date2013
Citation50th Inner Ear Biology Workshop (2013)
Abstract[Background]: Human IGF-I deficiency (ORPHA73272, OMIM608747) is a rare disease associated with poor growth rates, mental retardation and syndromic hearing loss. Equally, Igf1−/− mice are dwarfs with poor survival rates and congenital profound deafness1. IGF-I is a neuroprotective agent, and accordingly, low circulating IGF-I levels have been related to cognitive and brain alterations. Igf1−/− mice present undetectable serum levels of IGF-I throughout their life, whereas Igf1+/- and Igf1+/+ littermates show an agedependent decrease in IGF-I serum levels, especially from 6 months of age on2,3, which correlates with the increase in ABR thresholds. There is little information on the potential protective actions of IGF-I against noiseinduced hearing loss (NIHL). [Methods]: We have studied the susceptibility of Igf1+/- and Igf1+/+mice to NIHL at different ages, with functional (auditory brainstem responses, ABR), morphological (cochlear histology and stereological hair-cell quantification) and molecular (Western Blotting) studies. [Results]: Noise-exposure experiments with 3 months-old mice did not reveal differences between genotypes. However, 6 month-old Igf1+/- mice presented a greater susceptibility to noise damage, with higher threshold shifts and a poorer recovery compared to control mice. Igf1+/- mice showed severe morphological changes, as well as an altered intracellular signaling response to IGF-I. These changes correlated with low IGF-I serum levels in the heterozygous mice, compared to wild type. [Conclusion]: These results support the idea that IGF-I-based therapies could contribute to prevent or ameliorate age-related and noise-induced hearing loss.
DescriptionPóster presentado en el 50th Inner Ear Biology Workshop (IEB), celebrado en Alcalá de Henares del 10 al 13 de septiembre de 2013.-- Tambien presentado al ARO 36th Annual MidWinter Meeting, celebrado en baltimore (US) del 16 al 20 de febrero de 2013.
Appears in Collections:(IIBM) Comunicaciones congresos
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