aminoglycoside antibiotics hearing loss metabolic imaging nicotinamide adenine dinucleotide nicotinamide adenine dinucleotide phosphate ototoxicity Paper Special Section Papers two-photon microscopy
Aminoglycoside antibiotics are implicated as culprits of hearing loss in more than 120,000 individuals annually. Research has shown that the sensory cells, but not supporting cells, of the cochlea are readily damaged and/or lost after use of such antibiotics. High-frequency outer hair cells (OHCs) show a greater sensitivity to antibiotics than high- and low-frequency inner hair cells (IHCs). We hypothesize that variations in mitochondrial metabolism account for differences in susceptibility. Fluorescence lifetime microscopy was used to quantify changes in NAD(P)H in sensory and supporting cells from explanted murine cochleae exposed to mitochondrial uncouplers, inhibitors, and an ototoxic antibiotic, gentamicin (GM). Changes in metabolic state resulted in a redistribution of NAD(P)H between subcellular fluorescence lifetime pools. Supporting cells had a significantly longer lifetime than sensory cells. Pretreatment with GM increased NAD(P)H intensity in high-frequency sensory cells, as well as the NAD(P)H lifetime within IHCs. GM specifically increased NAD(P)H concentration in high-frequency OHCs, but not in IHCs or pillar cells. Variations in NAD(P)H intensity in response to mitochondrial toxins and GM were greatest in high-frequency OHCs. These results demonstrate that GM rapidly alters mitochondrial metabolism, differentially modulates cell metabolism, and provides evidence that GM-induced changes in metabolism are significant and greatest in high-frequency OHCs.
Gentamicin differentially alters cellular metabolism of cochlear hair cells as revealed by NAD(P)H fluorescence lifetime imaging
Creators
Lyandysha V. Zholudeva - Drexel University
Kristina G. Ward - Creighton University
Michael G. Nichols - Creighton University
Heather Jensen Smith - Creighton University
Publication Details
Journal of biomedical optics, v 20(5), pp 051032-051032
Series
Special Section on Laser Applications in Life Sciences
Publisher
Society of Photo-Optical Instrumentation Engineers
Grant note
RO3DC012109 / National Institute on Deafness and Other Communication Disorders
R15GM085776 / MN
P20GM103471 / National Institute of General Medical Sciences
8P20GM103471-09 / COBRE
G20RR024001 / National Center for Research Resources of the National Institutes of Health
Resource Type
Journal article
Language
English
Academic Unit
Neurobiology and Anatomy
Web of Science ID
WOS:000356241900037
Scopus ID
2-s2.0-84923362945
Other Identifier
991019168149704721
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