Linked Life Data

17141999

Source:http://linkedlifedata.com/resource/pubmed/id/17141999

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-3-12
pubmed:abstractText
Pathologies of senescence, in particular those of neurosensory organs represent an important health problem. The improvement of the life expectation entails the fast increase of the frequency of the age-related hearing loss (ARHL) in the population. There are numerous factors that contribute to this process, which include altered vascular characteristics, hypoxia/ischemia, genetic mutations and production of reactive oxygen species. We were interested in understanding the mechanisms involved in the cochlear degeneration in a mouse model of ARHL, the cd/1 mice. Since in human, hypoxia/ischemia is an important pathogenetic factor for inner ear disease, the regulation of HIF-1 activity in the cochlea, the presence of radical oxygen species in the cochlea and its subsequent disturbances of cellular signaling cascades were investigated. In this study, we explored auditory function of cd/1 mice at the age of 4, 12 and 24 weeks and correlated it with the presence of oxidative damage in the cochlea, and cochlear HIF-1 responsive target genes regulation, involved in pathways promoting inflammation such as tumor necrosis factor (TNF-alpha), or cell death with the p53 protein, Bax protein and surviving factors with insulin-like growth factor-1 (IGF-1). After implantation of electrodes for auditory nerve acoustic thresholds measurements, we analyzed every cochlea. First, we confirmed that the cd/1 mice presented a characteristic profile of ARHL starting at 12 weeks of age. Then, according to our previous report [Riva, C., Longuet, M., Lucciano, M., Magnan, J., Lavieille, J.P., 2005. Implication of mitochondrial apoptosis in neural degeneration in a murin model for presbyacusis. Rev. Laryngol. Otol. Rhinol. 126 (2), 67-74], we noticed many alterations in the cochlea. Histologically, at 4 weeks, intensive HIF-1alpha expression was detected in the cochlea followed by ROS formation at 12 weeks, which may lead to cochlear degeneration and induction the onset of ARHL in the cd/1 mice model. In the cochlea, while the inner and the outer hair cells remained intact at 4 and 12 weeks, the spiral ganglion was more altered. Moreover, the Schwann cells of the spiral ganglion seemed to be more vulnerable to free radical damage than the neurons and degenerated more rapidly. The mechanisms of degeneration in the spiral ganglion involved a caspase-3 and Bax mediated-apoptosis via p53 protein accumulation. Since oxygen radicals are required for the post-translational stabilization of HIF-1alpha during hypoxia, the tandem " HIF-ROS " induced multiple reactions within the cochlea, like a strong inflammatory response with increased expression of TNF-alpha, and inhibition of neuronal protection mechanisms with repression of IGF-1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0531-5565
pubmed:author
pubmed:issnType
Print
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
327-36
pubmed:meshHeading
pubmed-meshheading:17141999-Action Potentials, pubmed-meshheading:17141999-Aging, pubmed-meshheading:17141999-Animals, pubmed-meshheading:17141999-Anoxia, pubmed-meshheading:17141999-Apoptosis, pubmed-meshheading:17141999-Caspase 3, pubmed-meshheading:17141999-Cochlea, pubmed-meshheading:17141999-Cochlear Nerve, pubmed-meshheading:17141999-Coloring Agents, pubmed-meshheading:17141999-Hearing Loss, pubmed-meshheading:17141999-Hypoxia-Inducible Factor 1, alpha Subunit, pubmed-meshheading:17141999-Immunohistochemistry, pubmed-meshheading:17141999-Injections, Intravenous, pubmed-meshheading:17141999-Insulin-Like Growth Factor I, pubmed-meshheading:17141999-Mice, pubmed-meshheading:17141999-Nitroimidazoles, pubmed-meshheading:17141999-Reactive Oxygen Species, pubmed-meshheading:17141999-Schwann Cells, pubmed-meshheading:17141999-Spiral Ganglion, pubmed-meshheading:17141999-Tumor Necrosis Factor-alpha, pubmed-meshheading:17141999-Tumor Suppressor Protein p53, pubmed-meshheading:17141999-Up-Regulation
pubmed:year
2007
pubmed:articleTitle
Age-related hearing loss in CD/1 mice is associated to ROS formation and HIF target proteins up-regulation in the cochlea.
pubmed:affiliation
Laboratoire d'Otologie Neuro-otologie et Micro-Endoscopie, IFR Jean Roche, Faculté de Médecine Nord, Université de la Méditerranée, Bd Pierre Dramard, Marseille, France. riva-lavieille.c@jean-roche.univ-mrs.fr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't