Degree Name

Master of Science

Document Type

Thesis

Date Created

5-1-2021

Department

College of Natural and Health Sciences, Chemistry and Biochemistry, Chemistry and Biochemistry Student Work

Embargo Date

5-7-2022

Abstract

Excessive exposure to noise leads to hearing loss but the mechanism by which this happens remains unknown. Presently, dopamine, a neurotransmitter widely known for its involvement in learning and reward-based actions, has also been linked to auditory processes in the inferior colliculus, a principal integration center for hearing and related processes. Preliminary data from our research laboratory, has demonstrated that exposure to deafening noise leads to decreased dopamine release in the inferior colliculus, thus implicating the dopamine system in hearing loss. One plausible mechanism underlying this noise-induced alteration in dopamine neurotransmission could be via excessive production of reactive oxygen species (ROS). Reactive oxygen species can also modulate synaptic transmission. Thus, we hypothesize that loud noise would trigger overproduction of ROS, specifically hydrogen peroxide (H2O2) and in turn attenuate dopamine release in the inferior colliculus. Since excessive production of H2O2 could result in the depletion of adenosine triphosphate (ATP), we also evaluate the effect of the noise exposure on ATP levels. In order to determine the effect of deafening noise on proteins that regulate dopamine synthesis, we analyze biometals that act as prosthetic groups and may be involved in protein coordination and neurotransmission. The present work utilizes colorimetric assays and XRF analysis to examine changes in H2O2, ATP and biometal concentrations of Fe, Ca, K and Zn in the inferior colliculus of adult Sprague Dawley rats following exposure to loud noise. Finally, we explore the possibility of minimizing the effect of noise through antioxidant (α-lipoic acid) administration (50 mg/kg -I. P). The results of this study demonstrate that loud noise significantly increases the production of H2O2 (p < 0.0001, n = 10 rats/group). However, the noise exposure had no significant effect on ATP levels (p = 0.5850, 10 rats/group). Furthermore, noise exposure caused a significant increase in Fe, Ca and K levels (n = 5 rats/group). The administration of the antioxidant, α-lipoic acid reduced the concentration of H2O2 in the noise exposed group (p < 0.0001, n = 9 rats/group) and restores biometal concentration for Fe, Ca and K (n = 5 rats/group) to levels comparable with the control but has no effect on ATP. These results expand our understanding on the involvement of dopamine in deafness related changes in the inferior colliculus and open doors to further explore neural mechanisms underlying dopamine’s involvement in hearing.

Keywords

Reactive Oxygen Species; Hydrogen Peroxide; Adenosine Triphosphate; Dopamine; -Lipoic Acid; Inferior Colliculus; Noise; Hearing Loss; Auditory System; Biometals

Rights Statement

Copyright is held by the author.

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