Cu/Zn SOD deficiency potentiates hearing loss and cochlear pathology in aged 129,CD-1 mice.
Copper/zinc superoxide dismutase (Cu/Zn SOD) is a first-line defense against free radical damage in the cochlea and other tissues. To determine whether deficiencies in Cu/Zn SOD increase age-related hearing loss and cochlear pathology, we collected auditory brainstem responses (ABRs) and determined cochlear hair cell loss in 13-month-old 129/CD-1 mice with (a) no measurable Cu/Zn SOD activity (homozygous knockout mice), (b) 50% reduction of Cu/Zn SOD (heterozygous knockout mice), and (c) normal levels of Cu/Zn SOD (wild-type mice). ABRs were obtained by using 4-, 8-, 16-, and 32-kHz tone bursts. Cochleas were harvested immediately after testing, and separate counts were made of inner and outer hair cells. Compared with wild-type mice, homozygous and heterozygous knockout mice exhibited significant threshold elevations and greater hair cell loss. Phenotypic variability was higher among heterozygous knockout mice than among wild-type or homozygous knockout mice. Separate groups of wild-type and homozygous knockout mice were examined for loss of spiral ganglion cells and eighth nerve fibers. At 13 months of age, both wild-type and knockout mice had significantly fewer nerve fibers than did 2-month-old wild-type mice, with significantly greater loss in aged knockout mice than in aged wild-type mice. Thirteen-month-old knockout mice also had a significant loss of spiral ganglion cells compared with 2-month-old wild-type mice. The results indicate that Cu/Zn SOD deficiencies increase the vulnerability of the cochlea to damage associated with normal aging, presumably through metabolic pathways involving the superoxide radical.
McFadden
S L
SL
Center for Hearing and Deafness, State University of New York, Buffalo, New York 14214, USA. mcgadden@acsu.buffallo.edu
Ding
D
D
Burkard
R F
RF
Jiang
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H
Reaume
A G
AG
Flood
D G
DG
Salvi
R J
RJ
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002452:Cell Count; D003051:Cochlea / Q000201:enzymology*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005260:Female; D006199:Hair Cells, Auditory, Inner / Q000201:enzymology / Q000473:pathology; D018072:Hair Cells, Auditory, Outer / Q000201:enzymology / Q000473:pathology; D034381:Hearing Loss / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009412:Nerve Fibers / Q000201:enzymology; D013136:Spiral Ganglion / Q000201:enzymology / Q000473:pathology; D013482:Superoxide Dismutase / Q000172:deficiency*
D013482:Superoxide Dismutase