Stress Response and Hearing Loss Differentially Contribute to Dynamic Alterations in Hippocampal Neurogenesis and Microglial Reactivity in Mice Exposed to Acute Noise Exposure

Abstract

Noise-induced hearing loss (NIHL) is one of the most prevalent forms of acquired hearing loss, and it is associated with aberrant microglial status and reduced hippocampal neurogenesis; however, the nature of these associations is far from being elucidated. Beyond its direct effects on the auditory system, exposure to intense noise has previously been shown to acutely activate the stress response, which has increasingly been linked to both microglial activity and adult hippocampal neurogenesis in recent years. Given the pervasiveness of noise pollution in modern society and the important implications of either microglial activity or hippocampal neurogenesis for cognitive and emotional function, this study was designed to investigate how microglial status and hippocampal neurogenesis change over time following acoustic exposure and to analyze the possible roles of the noise exposure-induced stress response and hearing loss in these changes. To accomplish this, adult male C57BL/6J mice were randomly assigned to either a control or noise exposure (NE) group. Auditory function was assessed by measuring ABR thresholds at 20 days post noise exposure. The time-course profile of serum corticosterone levels, microglial status, and hippocampal neurogenesis during the 28 days following noise exposure were quantified by ELISA or immunofluorescence staining. Our results illustrated a permanent moderate-to-severe degree of hearing loss, an early but transient increase in serum corticosterone levels, and time-dependent dynamic alterations in microglial activation status and hippocampal neurogenesis, which both present an early but transient change and a late but enduring change. These findings provide evidence that both the stress response and hearing loss contribute to the dynamic alterations of microglia and hippocampal neurogenesis following noise exposure; moreover, noise-induced permanent hearing loss rather than noise-induced transient stress is more likely to be responsible for perpetuating the neurodegenerative process associated with many neurological diseases.

Noise exposure in early adulthood causes age-dependent and brain region-specific impairments in cognitive function

“…Taken together, the results from the 18day visuomotor associative learning task show no effect of occupational-like noise exposure on the rats' overall accuracy, but a faster reaction time in the first few weeks post-noise exposure. Noise exposure altered microglial density in the hippocampus, but not the auditory cortex or striatum Previous studies have implicated a role for altered microglial expression in noise-induced brain pathology in the auditory pathway (Baizer et al, 2015;Fuentes-Santamaria et al, 2017;Wang et al, 2019) and hippocampus (Cui et al, 2015;Zhuang et al, 2020;Li et al, 2021). To determine if noise exposure alters the profile of microglia in a brain region-specific manner across aging, we carried out immunolabeling of the microglial protein ionized calcium binding adaptor molecule 1 (Iba1) and quantified its expression in the auditory cortex, hippocampus, and striatum using two metrics (Figure 5).…”

“…Previous studies have implicated a role for altered microglial expression in noise-induced brain pathology in the auditory pathway ( Baizer et al, 2015 ; Fuentes-Santamaria et al, 2017 ; Wang et al, 2019 ) and hippocampus ( Cui et al, 2015 ; Zhuang et al, 2020 ; Li et al, 2021 ). To determine if noise exposure alters the profile of microglia in a brain region-specific manner across aging, we carried out immunolabeling of the microglial protein ionized calcium binding adaptor molecule 1 (Iba1) and quantified its expression in the auditory cortex, hippocampus, and striatum using two metrics ( Figure 5 ).…”

“…These time-dependent changes in microglia warrant additional consideration, as ours is the first study to report that it took several months, not just days/weeks, following the noise exposure before the decrease in hippocampal microglial cell density emerged. Second, as past studies have suggested that noise-induced changes in microglial expression cause hippocampal dysfunction (e.g., impaired neurogenesis) (Zhuang et al, 2020;Li et al, 2021), we investigated whether noise-induced changes in microglial expression contributed to the extent of cognitive impairment 10.3389/fnins.2022.1001686 following our occupational-like noise exposure. To that end, we performed a linear regression between hippocampal microglial density and the 13-month-old rats' cumulative average time to reach the hidden platform in the Morris water maze.…”

“…If this state persists, as commonly seen in aging and neurological disorders, chronically activated microglia are hypothesized to play a neurotoxic role, releasing proinflammatory cytokines, and contributing to neural degradation (Block et al, 2007). Of concern, alterations in microglial expression have also 10.3389/fnins.2022.1001686 been observed in the hippocampus of noise-exposed rodents and these immune cells have been theorized to underly the cognitive impairments commonly seen following noise exposure (Zhuang et al, 2020;Li et al, 2021). However, no studies have examined if noise-induced alterations in microglial expression occur in other cognitive brain regions, such as the striatum, further contributing to impairments in cognitive function.…”

“…Previous investigations into the link between hearing loss and cognitive impairment in animal models have utilized methodological approaches that may limit their translatability for noise-induced hearing loss in humans. For example, many of these experimental studies have employed intense noise exposures, in excess of 120 dB SPL, that cause severe hearing loss or deafness; an approach that does not closely resemble the most common forms of noise-induced hearing loss resulting from environmental, recreational, and occupational settings ( Kraus et al, 2010 ; Tao et al, 2015 ; Liu et al, 2016 , 2018 ; Zhuang et al, 2020 ; Li et al, 2021 ). Furthermore, many studies have investigated cognitive function in the immediate days or weeks following noise exposure ( Cui et al, 2009 ; Cheng et al, 2011 ; Wang et al, 2016 ), highlighting the need to determine if noise-induced cognitive impairments persist across aging.…”