NORA Manufacturing Sector Strategic Goals
R013973 - 021H: Adverse Effects of Noise on Hearing: Basic Mechanisms (3973)Start Date: 9/15/2008
End Date: 9/14/2011
Principal Investigator (PI)Name: Viji Potula
Funded By: NIOSH
Primary Goal Addressed4.0
Secondary Goal AddressedNone
Attributed to Manufacturing50%
The research is aimed at identifying the fundamental ways in which exposure to moderate levels of noise damages cells in the OC and produces PTS. It has been known for several decades that hair-cell loss precedes measurable PTS. Thus, strategies must be developed to preserve the structure of the OC, including the hair-cell population, rather than simply preserving audiometric thresholds. To be successful, strategies for reducing the incidence and magnitude of NIHL in the general population will depend upon elucidating the mechanisms of noise-induced damage to the OC. Thse studies are designed to determine the initial event(s) that lead to noise-induced hair-cell death. This information is important so that a focused search can be conducted for effective treatment strategies that will minimize noise-induced hair-cell death or will rescue noise-damaged hair cells before they pass 'the point of no return.' In this research, they will test the functional and structural effects of one exogenously applied ROS (i.e., hydrogen peroxide generating the hydroxyl radical).
At least 30 million Americans are exposed to excessive noise daily with many sustaining permanent noise-induced hearing loss (NIHL). The costs for NIHL add to billions of dollars per year. Despite the relevance of noise to human health and a long history of noise research, we do not know how noise destroys cells in the organ of Corti (OC). Based on animal studies, several theories on mechanisms of noise damage have been developed, but none proven unequivocally. It is not known why noise causes different patterns of cell loss in the apical and basal OC. The lack of knowledge about mechanisms of cell death from noise has hindered identification of noise-protective agents. We discovered that some dying outer hair cells (OHCs) in noiseexposed cochleae have morphological appearances that are distinct from apoptosis, oncosis and autophagy. If this newly discovered pathway dominates OHC death following moderate exposures, this will revolutionize thinking about the mechanisms of noise damage. Our proposed studies will determine what death pathways cochlear hair cells follow after chinchillas are exposed to typical workplace noise [i.e., 4-kHz octave band of noise (OBN) or 0.5-kHz OBN at 92-95 dB SPL]. With Specific Aim #1, the apex-to-base patterns and types of cell death and their timing will be determined at 0-30 days post-exposure. Changes in auditory function will be determined using auditory brainstem response, compound action potential and cochlear microphonic thresholds. The vital dye, trypan blue, will be instilled into one of the cochlear fluid spaces in-vivo in order to identify cells with disrupted plasma membranes. With Specific Aim #2, we will determine the site of action for free-radial damage to OHC plasma membranes compared to the damage produced by noise. Fixed cochleae will be embedded in plastic and dissected as flat preparations. Differential counts of missing and dying hair cells will be made and cells with trypan-blue-stained nuclei will be counted throughout the cochlea. We will compare changes in auditory function to losses of hair cells and other types of structural damage. Our results will provide information on mechanisms of damage from moderate noise so that drugs can be developed that will prevent or minimize noise-induced cell death.
Specific Aim #1. Quantitatively determine the death pathways followed by dying hair cells at 0, 7, 14 and 30 days post-exposure in chinchillas after a moderate-level noise exposure that results in a moderate temporary threshold shift (TTS) and often, a permanent threshold shift (PTS).