Investigation of Notch Signaling during Spontaneous Regeneration of Cochlear Hair Cells
Abstract
Hearing loss and tinnitus commonly occur after exposure to intense or prolonged levels of loud noise which are inherent to military settings. These noise exposures cause hearing loss by damaging specialized cells in the inner ear. These cells, called hair cells, have unique cilia (or hairs) on their surface that detect sound vibrations, which are transmitted to the brain for perception of speech, music, and other sounds. Once hair cells are killed, they are not replaced and permanent hearing loss ensues. High-level noise exposure is also the most common cause of tinnitus. When hair cells are killed, it causes a loss of auditory signals to the brain. The brain tries to compensate by making changes in its connections, but this can generate phantom sounds that are associated with tinnitus such as ringing in the ears. In addition, the blast wave, which causes traumatic brain injury, also kills hair cells and can result in hearing loss and/or tinnitus. Current treatment strategies for hearing loss, such as hearing aids and cochlear implants, provide some benefit but do not restore normal hearing and are inadequate for many military deployments and work settings. There are also no Food and Drug Administration-approved drugs for the treatment of these disorders. Thus, there is a compelling need for further research and additional treatment strategies for hearing loss and tinnitus. In contrast to humans and other mammals, birds, fish, and amphibians can regenerate their hair cells after damage and restore hearing. New hair cells are derived from neighboring cells that either first divide and then become a hair cell or directly change into a hair cell without cell division. We have recently discovered that newborn mice can also regenerate their hair cells after damage. This offers the opportunity to study the hair cell regeneration process in a mammal, which is much closer to humans than birds and fish. Understanding the genes and proteins involved in the hair cell regeneration process in young mice is a first step to stimulating successful hair cell regeneration in adult mice and translating these findings to humans who suffer from hearing loss. In addition, hearing aids, which restore auditory signals from the inner ear, have been shown to partially suppress tinnitus perception and thus hair cell regeneration could also be used as a treatment strategy for tinnitus. Proposed studies will investigate the Notch signaling pathway that has a well-defined role in the development of hair cells and have been implicated in the hair cell regeneration process that occurs in birds, fish, and amphibians. We will use our new model of spontaneous hair cell regeneration in newborn mice to understand the role of the Notch signaling pathways in the hair cell regeneration process. Our long-term goal is to replace hair cells and restoring auditory signals to the brain and thus the proposed studies are relevant to both hearing loss and tinnitus. Military personnel have a much higher rate of hearing loss than the general population due to the noisy environment that they are exposed to. In addition, acute blast or traumatic brain injury can also cause hearing loss. While hearing loss is not a life-threating condition in most situations, when it interferes with understanding military commands, it can result in death. Successful completion of the proposed studies will provide insight into the genes and proteins that control hair cell regeneration in mammals. This information can then be used to develop drugs to restore hearing and treat tinnitus in Soldiers, Veterans, and others suffering from hearing loss.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 29, 2016
- Source ID
- W81XWH1510475
Entities
People
- Brandon C Cox
Organizations
- Southern Illinois University School of Medicine
- United States Army