Cognitive, neurophysiological, and molecular alterations following noise-induced hearing loss

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