Doctor of Philosophy (Ph.D.)
Degree Granting Department
Robert Frisina, Ph.D.
Joseph Walton, Ph.D.
William Lee III, Ph.D.
Mark Jaroszeski, Ph.D.
Bo Ding, M.D.
ABR, Glutamate, Hair cell, mGlu7, NIHL
Hearing loss due to exposure to high level sound is a major health problem that causes permanent hearing impairment and has a significant impact on job productivity and quality of life. A large population suffers from noise-induced hearing loss (NIHL), a disorder for which there is currently no FDA-approved prevention, treatment or cure. The goal of my dissertation work is to provide insights into the effects of noise trauma on hearing abilities of normal hearing subjects, and determine how a new therapeutic compound (mGlu7 modulator) can protect and/or prevent loss of, or damage to sensory cells and brain neurons, including hair cells and auditory nerve fibers, due to glutamate synaptic activity hyper-excitation.
NIHL can be induced by damaging the cochlear organ of Corti; as well as hypoxia of the inner ear due to reduced blood flow; oxidative stress related to the buildup of reactive oxygen species (ROS); and neural degeneration of synaptic terminals of cochlear nerve fibers and spiral ganglion cells . It is known that membrane proteins called metabotropic glutamate receptors (mGluRs) regulate synaptic neurotransmission of glutamate and helps control ionic homeostasis, and they can be activated by release of glutamate from pre-synaptic cells, such as the hair cells of the inner ear.
I studied the effects of a new drug that modulates mGlu7 receptors and their activity in the auditory system and investigated its effects on noise-induced hearing loss (NIHL) in a rodent animal model. We achieved this by exposing mice to a loud noise trauma, then assessing the effects of the trauma using a series of hearing tests and biomarker studies. Known physiological indicators of NIHL in rodents, such as a change in the evoked response threshold, the reduced amplitude, increased latency of the auditory brainstem response (ABR) waves in response to noise trauma, were used to provide further insights into the overall progression of NIHL. We used ABR wave analysis to examine the responses of different levels of the auditory pathway to tone and noise burst stimuli; and distortion product otoacoustic emissions (DPOAEs) were used to examine the functionality of the outer hair cell system; and a gap-in-noise (GIN) paradigm was utilized to examine changes in auditory temporal processing due to noise damage. NIHL can also alter neurophysiological responses in the central auditory system; here we investigated effects of acoustic overstimulation on key structures in the parts of the brain used for hearing, including the cochlear nuclei (CN) and inferior colliculus (IC).
Scholar Commons Citation
Amanipour, Reza, "Rescue of Hearing and Protection of Auditory Structures from Noise-Induced Hearing Loss" (2019). Graduate Theses and Dissertations.