Cu/Zn superoxide dismutase and age-related hearing loss.
Mice, in which the genetics can be manipulated and the life span is relatively short, enable evaluation of the effects of specific gene expression on cochlear degeneration over time. Antioxidant enzymes such as Cu/Zn superoxide dismutase (SOD1) protect cells from toxic, reactive oxygen species and may be involved in age-related degeneration. The effects of SOD1 deletion and over-expression on the cochlea were examined in Sod1-null mice, Sod1 transgenic mice and in age- and genetics-matched controls. Auditory brainstem responses (ABR) were measured and cochleae were histologically examined. The absence of SOD1 resulted in hearing loss at an earlier age than in wildtype or heterozygous mice. The cochleae of the null mice had severe spiral ganglion cell degeneration at 7-9 months of age. The stria vascularis in the aged, null mice was thinner than in the heterozygous or wildtype mice. Over-expression of SOD1 did not protect against hearing loss except at 24 months of age. In conclusion, SOD1 seems important for survival of cochlear neurons and the stria vascularis, however even half the amount is sufficient and an over abundance does not provide much protection from age-related hearing loss.
Keithley
Elizabeth M
EM
Division of Otolaryngology - Head and Neck Surgery, University of California, San Diego, La Jolla, 92093-0666, USA. ekeithley@ucsd.edu
Canto
Cecilia
C
Zheng
Qing Yin
QY
Wang
Xiaobo
X
Fischel-Ghodsian
Nathan
N
Johnson
Kenneth R
KR
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D001933:Brain Stem / Q000502:physiology; D003051:Cochlea / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D034381:Hearing Loss / Q000201:enzymology* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009925:Organ of Corti / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D011304:Presbycusis / Q000503:physiopathology; D013136:Spiral Ganglion / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D013316:Stria Vascularis / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000235:genetics*; D000072105:Superoxide Dismutase-1
C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1