Chronic Noise Exposure Acts Cumulatively to Exacerbate Alzheimer’s Disease-Like Amyloid-β Pathology and Neuroinflammation in the Rat Hippocampus

Abstract

A putative etiological association exists between noise exposure and Alzheimer's disease (AD).Amyloid-β (Aβ) pathology is thought to be one of the primary initiating factors in AD. It has been further suggested that subsequent dysregulation of Aβ may play a mechanistic role in the AD-like pathophysiology associated with noise exposure. Here, we used ELISA, immunoblotting, cytokine arrays, and RT-PCR, to examine both hippocampal Aβ pathology and neuroinflammation in rats at different time points after noise exposure. We found that chronic noise exposure significantly accelerated the progressive overproduction of Aβ, which persisted for 7 to 14 days after the cessation of exposure. This effect was accompanied by up-regulated expression of amyloid precursor protein (APP) and its cleavage enzymes, β-and γ-secretases. Cytokine analysis revealed that chronic noise exposure increased levels of tumor necrosis factor-α and the receptor for advanced glycation end products, while decreasing the expression of activin A and platelet-derived growth factor-AA. Furthermore, we found persistent elevations of glial fibrillary acidic protein and ionized calciumbinding adapter molecule 1 expression that closely corresponded to the noise-induced increases in Aβ and neuroinflammation. These studies suggest that lifelong environmental noise exposure may have cumulative effects on the onset and development of AD.People are increasingly exposed to environmental noise from many sources including work, traffic, media, and household appliances. Long-term noise exposure increases the risk of physical damage and is considered a health hazard 1 . Such exposure can have physiological or even pathological effects on the classical auditory system, as well as non-lemniscal brain regions such as the hippocampus and cerebral cortex. Studies therefore suggest that chronic noise exposure may induce abnormal auditory input to the brain resulting in aberrant changes in the hippocampus and cortex 2-7 . It has been reported, for instance, that such exposure results in the persistent tau pathology observed in Alzheimer's disease (AD) 2,4,[7][8][9] . In the hippocampus, excitotoxic and metabolic insults can ultimately result in memory loss 3 . Considering

Effects of chronic noise on glucose metabolism and gut microbiota–host inflammatory homeostasis in rats

“…In our recent study, we demonstrated reciprocal activation of pro-inflammatory cytokines and astrocytes after noise exposure, which could cause a positive feedback loop that results in central nervous system abnormalities3. Resident microbiota regulate gut inflammation41.…”

“…Long-term noise exposure is considered as a health hazard1 and has been linked to non-auditory effects, including Alzheimer’s disease-like neuropathology23 and metabolic disorders4. Recent epidemiological studies have shown that chronic noise exposure is associated with increased risk of adiposity56, higher levels of cholesterol7 and development of diabetes8.…”

Environmental noise induces the release of stress hormones and inflammatory signaling molecules leading to oxidative stress and vascular dysfunction—Signatures of the internal exposome

“…More specifically, chronic noise altered the percentage of Proteobacteria (e.g., Escherichia, Salmonella, Helicobacter, and Yersinia) and Actinobacteria in the gut, increasing Roseburia but decreasing Faecalibacterium levels in the cecum relative to controls, all of which may explain noiseinduced impairment of glucose handling with a shift to prediabetic conditions (or metabolic syndrome) as well as intestinal inflammation [87]. Also neuroinflammation and Alzheimer's disease pathology was aggravated by noise exposure in a rat model [88]. These observations are in accordance with our own observations that low-level noise exposure induces increased circulating cytokines and infiltration of immune cells of the vasculature (Fig.…”

Transcriptome analysis of the hippocampus in environmental noise-exposed SAMP8 mice reveals regulatory pathways associated with Alzheimer’s disease neuropathology

“…Hippocampus preparation and Western blot were performed as described previously [13,20]. Briefly, each hippocampus was dissected immediately after sacrificing the animal and was stored at − 80°C until use.…”

“…Real-time PCR was performed as previously described [20]. The hippocampus tissues from the exposure and control group mice were homogenized using a rapidly oscillating masher.…”