The proximate cause of sensorineural hearing loss is the death of irreplaceable cochlear hair cells, but the underlying basis of the selective vulnerability of hair cells to a variety of traumas and diseases is unknown. A prominent theory is the inability of hair cells to cope with metabolic demands, which would thereby trigger mitochondrial caspase- mediated apoptosis, but evidence for this theory is indirect. As we here show, it is now possible to assess the state of oxidative metabolism in hair cell mitochondria from the emissions of reduced nicotine adenine dinucleotide, an intermediate in oxidative phosphorylation. This proposal seeks support to develop application of this imaging technique to the problem of metabolic imaging in hair cells. We further request support to test the hypothesis that known differences in the vulnerability of cochlear outer hair cells compared to inner hair cells, and of basal turn hair cells compared to apical turn hair cells, correlate with differences in metabolic responses in the respective hair cell populations. The proposed development and experiments, we believe, represent the first steps in a new era of quantitation of oxidative metabolism in living hair cells that will greatly add to our understanding of many aspects of normative and pathological cochlear physiology.

Public Health Relevance

Narrative Deafness is a major cause of disability in the population and is likely to increase in significance as the population ages. The major form of deafness, called sensorineural, involves the loss of irreplaceable hair cells, which may be due to an inability to cope with metabolic challenges. Our project is to evaluate a new method of quantifying the metabolic state of living hair cells. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DC008995-01A1
Application #
7470876
Study Section
Auditory System Study Section (AUD)
Program Officer
Cyr, Janet
Project Start
2008-03-03
Project End
2010-02-28
Budget Start
2008-03-03
Budget End
2009-02-28
Support Year
1
Fiscal Year
2008
Total Cost
$212,207
Indirect Cost
Name
Creighton University
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
053309332
City
Omaha
State
NE
Country
United States
Zip Code
68178
Tiede, LeAnn; Steyger, Peter S; Nichols, Michael G et al. (2009) Metabolic imaging of the organ of corti--a window on cochlea bioenergetics. Brain Res 1277:37-41