The Role of Inflammatory Reponse in Noise-Induced Hearing Loss

Research Trainee: Takashi Shimano, MD, Postdoctoral Fellow, Dept. of Anatomy and Cell Biology at Wayne State University

Faculty Researcher: Tzy-Wen Gong, PhD, Research Investigator, Dept. of Otolaryngology at the University of Michigan

Noise-induced hearing loss is a wide-spread problem in industrialized society. Exposure to an intense loud noise disturbs the inner ear and normal hearing, causes irreversible damage to the delicate sensory epithelium of the cochlea and results in necrotic and apoptotic cell death (permanent threshold shift or PTS). On the other hand, exposure to a mild noise causes a smaller degree of hearing loss recovered within 7-10 days (temporary threshold shift or TTS). While TTS noise is thought to cause minor, reversible mechanical damage without significant cell death, PTS noise is thought to cause substantial, irreversible metabolic disturbance. However, our recent finding suggests that while TTS and PTS evoke many different changes at the molecular level, there are many shared changes.

We are interested in the molecular mechanisms that distinguish TTS from PTS responses. We hypothesize that PTS noise and TTS noise evoke different responses in a set of key regulators that lead to very different outcomes. TTS causes temporary imbalance of metabolic homeostasis that is either reversible or does not summate to long-lasting deterioration. In PTSexposed cochleae, activation or inhibition of these key regulators over-rides other signals that lead to irreversible reactions and cell death. Our long term objective is to identify critical regulatory mechanisms leading to irreversible changes and permanent damage and to identify molecular events underlying conditioning protection associated with TTS. Our preliminary study in a rat model of noise-induced hearing loss showed that tumor necrosis factor (TNF) signaling pathway is activated after PTS noise, but not TTS noise.