The conversion of sound into a neural signal is a result of neurotransmitter release from mechanically stimulated auditory hair cells and is regulated in part by efferent neuronal feedback. Suprathreshold mechanical or neurochemical stimuli are thought to initiate adaptive processes in the cochlea and may activate intracellular regulatory mechanisms that result in changes in the pattern and rate of gene expression. Such changes in gene expression allow a cell to respond to prolonged or potentially damaging stimuli in s specific and organized manner. The transcription factors designated CREB and CREM are one of the primary means by which extracellular stimuli control the rate of gene expression. Increases in cyclic AMP, calcium or other intracellular messengers result in the activation of CREB and CREM, which in turn bind to specific DNA sequence elements on target genes. This initial sequence of events is the driving force for the regulated expression of numerous genes. The proposed research will examine activation and expression patterns of CREB and CREM in the gerbil cochlea in order to characterize pathways for genetic control mechanisms and to test the hypothesis that sound at damaging intensities triggers CREB and CREM-mediated gene regulation the initial Specific Aim is the analysis of activated CREB in the noise-exposed cochlea by immunochemical techniques. In situ hybridization will then be used to achieve the second Specific Aim: the cellular localization of induced expression of the ICER isoform of CREM, gene known to be regulated by CREB. These studies will provide information needed to provide rationale for the prevention and treatment of noise-induced hearing loss.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Small Research Grants (R03)
Project #
1R03DC003535-01A1
Application #
2650269
Study Section
Special Emphasis Panel (ZDC1-SRB-F (15))
Project Start
1998-05-01
Project End
2001-04-30
Budget Start
1998-05-01
Budget End
1999-04-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425