Age-related hearing disorders include decreased pure tone perception and poor speech comprehension during background noise. There is some evidence suggesting that cholinergic pathways to the cochlear nucleus, the first brain center of the auditory system, may play a role in the recognition of signals in a noisy background. Studies of other central nervous disorders such as Alzheimer's disease have indicated age-related loss of cholinergic neurons in the brain. In the auditory system, however, the influence of aging on the function of cholinergic pathways is poorly understood. This study aims to explore the possible involvement of cholinergic pathways to the cochlear nucleus in age-related hearing disorders. The CBA mouse has a slowly progressive hearing loss with a similar tone with a similar tone course as that in humans, after correction of life span. We hypothesize that this mouse model has progressive loss of cholinergic neurons in auditory centers, expressed as decreased activities of the enzyme for acetylcholine. Two experiments are proposed in this study: 1) comparison in young and aged animals of the activity of the enzyme for acetylcholine synthesis, choline acetyltransferase (ChAT), in the superior olivary complex, where many somata of cholinergic neurons in auditory centers, expressed as decreased activities of the enzyme for acetylcholine synthesis and changed sensitivities of neurons in the auditory pathway to acetylcholine. To acetylcholine synthesis, choline acetyltransferase (ChAT), in the major target of these cholinergic neurons; 2) comparison in young and aged animals of the sensitivities of cochlear nucleus neurons to acetylcholine-related drugs. Correlation of the results from this study and those from previous studies on hearing function of this mouse model may increase understanding of age-related hearing disorders and suggest new treatment directions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Small Research Grants (R03)
Project #
1R03AG018972-01
Application #
6286834
Study Section
Special Emphasis Panel (ZAG1-PCR-5 (O2))
Program Officer
Finkelstein, Judith A
Project Start
2001-01-01
Project End
2002-12-31
Budget Start
2001-01-01
Budget End
2002-12-31
Support Year
1
Fiscal Year
2001
Total Cost
$73,500
Indirect Cost
Name
University of Toledo
Department
Surgery
Type
Schools of Medicine
DUNS #
807418939
City
Toledo
State
OH
Country
United States
Zip Code
43614