Thesis Format
Integrated Article
Degree
Doctor of Philosophy
Program
Anatomy and Cell Biology
Supervisor
Allman, Brian L.
2nd Supervisor
Whitehead, Shawn N.
Co-Supervisor
Abstract
Hearing loss is one of the most prevalent, chronic health conditions worldwide, with excessive exposure to loud noise as a leading cause. Beyond the devastating impact of hearing impairment itself, hearing loss has been associated with age-related cognitive impairment. Furthermore, it is well known that noise-induced hearing loss can lead to widespread plasticity in the central auditory pathway, and emerging evidence suggests that brain regions involved in higher-level cognitive functioning, such as the prefrontal cortex and hippocampus, are also affected. Thus, this thesis aims to investigate the cognitive, neurophysiological, and molecular alterations following noise-induced hearing loss using a rat model. Previously, we showed that the prefrontal cortex demonstrates noise-induced plasticity that is not present in the auditory cortex. Thus, in Chapter 2, we determined that impaired gamma phase coherence in the prefrontal cortex was associated with dendritic reorganization and decreased expression of proteins involved in GABAergic and glutamatergic neurotransmission in the prefrontal cortex; findings that were not observed in the auditory cortex, where gamma phase coherence remained unchanged post-noise exposure. In Chapter 3, to elucidate the link between hearing loss and age-related cognitive impairment, we investigated the effect of early-life noise exposure across aging. Our results indicated that not all brain regions appear equally susceptible to noise-induced hearing loss across aging, as noise exposure caused an age-specific deficit in hippocampal-dependent, but not striatal-dependent cognitive function. Furthermore, a subset of younger animals showed noise-induced deficits in spatial learning, suggesting that vulnerable subjects may be more susceptible to the effects of noise exposure. Given this finding, and emerging evidence that hearing loss represents a modifiable risk factor for dementia, we investigated if noise-induced hearing loss could exacerbate Alzheimer’s disease-related neuropathology and cognitive impairment in Chapter 4. Using a genetically susceptible model of Alzheimer’s disease, we observed that noise exposure caused changes that were dependent on genotype, sex, and cognitive domain, indicating a complex relationship between hearing loss and its effects on vulnerable subjects. Overall, this thesis identified novel findings related to the impact of noise-induced hearing loss on neurophysiological and molecular alterations in brain regions subserving cognitive function.
Summary for Lay Audience
Hearing loss is a prevalent and chronic health condition that negatively impacts one’s quality of life. Many individuals experience hearing damage following excessive exposure to loud noise at work, in the environment, or during recreational activities. Hearing damage itself is not the only problem facing noise-exposed individuals, as previous studies have identified detrimental changes in brain regions that are important for cognition. Furthermore, population studies have identified that hearing loss is a major risk factor for age-related cognitive decline, including dementia. Using a rat model, this thesis aimed to identify the effect of noise-induced hearing loss in brain regions that are important for cognitive function. One such region is the prefrontal cortex, where we identified impairments in sound processing following noise exposure, which were accompanied by structural and molecular changes in this brain region (Chapter 2). In contrast, the auditory cortex, another brain region where sound processing occurs, did not have these same impairments. Next, in Chapter 3, we investigated the effect of an early-life noise exposure across aging. We observed that not all cognitive functions were equally susceptible to the effects of noise exposure, as older rats showed impairments in spatial learning, but not associative learning. In addition, a subset of noise-exposed younger rats had impairments in spatial learning, leading us to believe that they may have been more vulnerable to the effects of noise-induced hearing loss. This finding was interesting given that hearing loss has recently been identified as a risk factor for Alzheimer’s disease. Thus, in Chapter 4, we investigated the effect of noise exposure on rats that were susceptible to developing brain damage and cognitive impairments consistent with patients suffering from Alzheimer’s disease. Our results indicated that the relationship between hearing loss and Alzheimer’s disease is complex, as noise exposure affected vulnerable rats in some brain regions, but not others, in a sex-dependent manner. Overall, the collective work in this thesis furthers our understanding of how noise-induced hearing loss affects the brain across aging and in vulnerable populations, as well as providing future avenues for research to elucidate the link between hearing loss and cognitive impairment.
Recommended Citation
Patel, Salonee, "Cognitive, neurophysiological, and molecular alterations following noise-induced hearing loss" (2023). Electronic Thesis and Dissertation Repository. 9813.
https://ir.lib.uwo.ca/etd/9813