title: Gene expression changes for antioxidants pathways in the mouse cochlea: relations to age-related hearing deficits.
abstract: Age-related hearing loss - presbycusis - is the number one neurodegenerative disorder and top communication deficit of our aged population. Like many aging disorders of the nervous system, damage from free radicals linked to production of reactive oxygen and/or nitrogen species (ROS and RNS, respectively) may play key roles in disease progression. The efficacy of the antioxidant systems, e.g., glutathione and thioredoxin, is an important factor in pathophysiology of the aging nervous system. In this investigation, relations between the expression of antioxidant-related genes in the auditory portion of the inner ear - cochlea, and age-related hearing loss was explored for CBA/CaJ mice. Forty mice were classified into four groups according to age and degree of hearing loss. Cochlear mRNA samples were collected and cDNA generated. Using Affymetrix® GeneChip, the expressions of 56 antioxidant-related gene probes were analyzed to estimate the differences in gene expression between the four subject groups. The expression of Glutathione peroxidase 6, Gpx6; Thioredoxin reductase 1, Txnrd1; Isocitrate dehydrogenase 1, Idh1; and Heat shock protein 1, Hspb1; were significantly different, or showed large fold-change differences between subject groups. The Gpx6, Txnrd1 and Hspb1 gene expression changes were validated using qPCR. The Gpx6 gene was upregulated while the Txnrd1 gene was downregulated with age/hearing loss. The Hspb1 gene was found to be downregulated in middle-aged animals as well as those with mild presbycusis, whereas it was upregulated in those with severe presbycusis. These results facilitate development of future interventions to predict, prevent or slow down the progression of presbycusis.
authors.affiliation: International Center for Hearing & Speech Research, National Technical Institute for the Deaf, Rochester Institute of Technology, Rochester, New York, United States of America ; Otolaryngology Dept., University of Rochester Medical School, Rochester, New York, United States of America.
authors.forename: Sherif F
authors.initials: SF
authors.lastname: Tadros
authors.affiliation: International Center for Hearing & Speech Research, National Technical Institute for the Deaf, Rochester Institute of Technology, Rochester, New York, United States of America ; Otolaryngology Dept., University of Rochester Medical School, Rochester, New York, United States of America.
authors.forename: Mary
authors.initials: M
authors.lastname: D'Souza
authors.affiliation: International Center for Hearing & Speech Research, National Technical Institute for the Deaf, Rochester Institute of Technology, Rochester, New York, United States of America ; Otolaryngology Dept., University of Rochester Medical School, Rochester, New York, United States of America ; Depts. Chemical & Biomedical Engineering, Communication Sciences & Disorders, and Global Center for Hearing & Speech Research, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Zhu
authors.affiliation: International Center for Hearing & Speech Research, National Technical Institute for the Deaf, Rochester Institute of Technology, Rochester, New York, United States of America ; Otolaryngology Dept., University of Rochester Medical School, Rochester, New York, United States of America ; Depts. Chemical & Biomedical Engineering, Communication Sciences & Disorders, and Global Center for Hearing & Speech Research, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Frisina
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D003051:Cochlea / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011304:Presbycusis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D054481:Thioredoxin Reductase 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D007521:Isocitrate Dehydrogenase; D005979:Glutathione Peroxidase; D054481:Thioredoxin Reductase 1; C516125:Txnrd1 protein, mouse