Prof. Isabel Varela-Nieto
Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) and CIBERER,
Instituto de Salud Carlos III, Madrid, Spain
Uncovering the factors involved in the progression of hearing loss associated ith aging: IGF-1 and beyond
Isabel Varela-Nieto, Blanca A. Cervantes and Lourdes Rodríguez de la Rosa
Insulin like growth factor type 1 (IGF-1) is an anti-neurodegenerative factor whose deficit causes profound human deafness. Epidemiological and experimental models studies have revealed a correlation between progressive hearing loss, cognitive decline and decreased plasma IGF-1 deficit. We have studied the cochlear expression of genes coding for IGF system and associated pathways, and the impact of knocking out Igf1 and downstream pathways genes during ageing and in the response to injury. Our results indicate that there is an age-dependent expression of these genes in the mouse cochlea. Being gene expression further regulated during the response to stress. The null mouse Igf1-/- is deaf and presents neurodegeneration of the spiral ganglion, among other functional and cellular alterations. In contrast, haploinsufficiency of IGF-1 did not cause an evident impact in the hearing acuity of young mice. However, following noise challenge, deficient mice showed increased threshold shifts and poorer recovery with time. Hearing loss was associated with increased cellular injury. Further analysis of molecular mechanisms of response to IGF-1 has been carried out in otic cell models.
In summary, our results suggest that IGF-1 plays a central role in cochlear homeostasis and that IGF-1 haploinsufficiency is a risk factor for hearing loss.
Supported by the EU FP7-IAPP2013-TARGEAR and Spanish FEDER/SAF AGEAR and HEARCODE projects.