%0 Journal Article
%T Hypoxia-inducible factor 1-alpha target protein up-regulation in Hypoxic cochlear neurons is associate with aged-related hearing loss in C57BL/6 mice
%A Emilie Donadieu
%A Catherine M. Riva
%J Ageing Research
%D 2012
%I 
%R 10.4081/ar.2012.e1
%X Molecular mechanisms underlining hypoxia- induced aged-hearing loss were studied. 3- months C57BL/6 mice were subjected to four weeks of hypoxia (10% 02), whereas, controls were kept under normoxic condition for up to six months. Auditory function was explored by CAP and Preyer¡¯s reflex measurements and correlated with histological analysis of the cochlea. The presence of oxidative damage, HIF-1 responsive target genes regulation involved in cell death, inflammation and neovascularization were assessed by immunofluorescence analysis. Hypoxia was associated to severe hearing loss at 4-8 and 16 KHz and degeneration of the cochlea, with significant cell loss (30%) in the spiral ganglion, the lateral wall, and the hair cells with a basal-apical alteration gradient. This was correlated with ROS formation and HIF-1a overexpression. Cochlear degeneration was due to apoptosis via activated caspase-3, P53, Bax and Bcl-2 protein differential expression in spiral ganglion, modiolus and spiral ligament. On the other hand, Hsp70, NF-kB transcription factor pathway and inflammatory mediators (caspase-1 and TNF-a) were induced in the stria vascularis. Furthermore, a phenomenon of neovascularization was observed with significant thickening of stria vascularis and increased expression of VEGF. In total, we demonstrated that the tandem-HIF-ROS is responsible for the caspase-3 and Bax¨Cmediated apoptosis via P53 protein accumulation in the cochlear neurons, while inflammatory response mediated by Hsp70 stress protein and NF-kB transcription factor generating a neovascularization phenomenon occurred in stria vascularis.
%K cochlear neurons
%K hearing loss
%K apoptosis
%K hypoxia
%K VEGF
%K ROS
%K HIF-1¦Á
%U http://www.pagepress.org/journals/index.php/ar/article/view/2094