Effects of Gentamicin on Cochlear Hair Cell Metabolism

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Authors
Tiede, Leann M.
Issue Date
2009-08-01
Type
Dissertation
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en_US
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Abstract
In the mammalian cochlea, hair cells convert the mechanical energy of sound to electrical signals in the auditory nerve, and are therefore an essential component of hearing. One cause of sensorineural hearing loss is through the loss of irreplaceable cochlear hair cells. Gentamicin, an effective antibiotic in the treatment of gram negative bacterial infections, is toxic to hair cells and therefore can result in permanent hearing loss. Gentamicin induces hair cell loss by triggering apoptosis, and therefore understanding metabolic events in hair cells during gentamicin treatment might provide information essential to the amelioration of the hair cell loss.|In this study, two-photon fluorescence confocal microscopy of the mitochondrial metabolic intermediate reduced nicotinamide adenine dinucleotide (NADH) was used to monitor changes in NADH concentration in mouse cochlear hair cells after the administration of gentamicin. The results demonstrated significant differences in the effects of gentamicin on NADH fluorescence levels in outer hair cells, compared to inner hair cells. Further evidence of fundamental differences in metabolism between outer and inner hair cells was provided by analysis of NADH fluorescence lifetimes. A gentamicin conjugated to the fluorescent dye Texas Red was used to show that uptake of gentamicin was similar in both hair cell types. The involvement of the mitochondrial permeability transition pore in the gentamicin was implicated using the pore blocking agent cyclosporine A. In striking contrast to current theories of gentamicin-mediated hair cell damage, gentamicin appears to reduce the production of free radicals in outer hair cells within the first half hour following uptake. As a whole, these studies suggest new approaches to the understanding of gentamicin-mediated hair cell damage as well as othertypes of sensorineural hearing loss.
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Creighton University
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Copyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.
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