10 - Investigating the effect of noise-induced hearing loss on microglial and cholinergic expression related to Alzheimer’s Disease in a rodent model

Poster Board Number: 10
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Odd poster #s – first hour
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Co-authors:

Salonee Patel - University of Western Ontario; Sarah Myers - University of Western Ontario; Sarah Hayes - University of Western Ontario; Shawn Whitehead - University of Western Ontario; Brian Allman - University of Western Ontario

Abstract Body :
Introduction: Dementia affects ~55 million people worldwide; a staggering statistic which highlights the need to limit its risk factors. Importantly, recent epidemiological studies have identified hearing loss as a major modifiable risk factor for the development of dementia, including AD. Further, preclinical studies have determined that noise-induced hearing loss causes molecular changes consistent with AD-related neuropathology (e.g. amyloid-beta production and tau hyperphosphorylation). However, the effect of noise-induced hearing loss on other AD-related neuropathology (e.g., cholinergic dysfunction, neuroinflammation) in models of genetic susceptibility remains unknown. Methods: To investigate the interplay of noise exposure and genetic susceptibility to AD, we utilized transgenic Fischer 344 (TgAPP) rats that overexpress pathogenic human amyloid precursor protein. At 12 months of age, male and female, TgAPP and wildtype rats were either noise- (100 dB SPL; 4 hours/day, 30 days) or sham-exposed. To investigate microglial morphology and density, immunohistochemical analyses of Iba1 expression was performed in the auditory cortex, hippocampus, and striatum. Additionally, cholinergic cell density was obtained using the immunohistochemical marker choline acetyltransferase (ChAT) in subregions of the basal forebrain, such as the medial septum (MS) and vertical diagonal band of Broca (vDB).Results: Consistent with the profile of hearing impairment often experienced by humans, our protocol resulted in a high-frequency hearing loss in the rats. As expected, TgAPP rats displayed significantly increased Iba1 cell density in the hippocampus and reduced cholinergic cell density in the MS; however, in contrast to our prediction, noise exposure did not exacerbate these results. Similar to previous studies from our lab, there was no evidence of noise-induced changes in microglial morphology, as assessed by soma/size ratio. Furthermore, noise exposure resulted in a significant reduction in cholinergic cells in the vDB, regardless of genotype. Lastly, a differential effect between sex and genotype was observed, such that noise-exposed wildtype male rats exhibited decreased striatal Iba1 cell density compared to their sham-exposed counterparts, whereas the noise-exposed TgAPP rats showed a significantly increased striatal Iba1 cell density. Conclusion/Significance: Our findings point to a complex relationship between noise-induced hearing loss and the progression of AD-related neuropathology in a genetically susceptible model; findings which support the need for proper auditory health as a preventative measure for AD.Funding Sources: Royal National Institute for Deaf People (RNID)