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. 2018 Jun 22;15(1):190.
doi: 10.1186/s12974-018-1223-4.

Effects of Chronic Noise Exposure on the Microbiome-Gut-Brain Axis in Senescence-Accelerated Prone Mice: Implications for Alzheimer's Disease

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Free PMC article

Effects of Chronic Noise Exposure on the Microbiome-Gut-Brain Axis in Senescence-Accelerated Prone Mice: Implications for Alzheimer's Disease

Bo Cui et al. J Neuroinflammation. .
Free PMC article

Abstract

Background: Chronic noise exposure is associated with neuroinflammation and gut microbiota dysregulation and increases the risk of Alzheimer's disease (AD). Environmental hazards are also thought to be associated with genetic susceptibility factors that increase AD pathogenesis. However, there is limited experimental evidence regarding the link between chronic noise stress and microbiome-gut-brain axis alterations, which may be closely related to AD development.

Methods: The aim of the present study was to systematically investigate the effects of chronic noise exposure on the microbiome-gut-brain axis in the senescence-accelerated mouse prone 8 (SAMP8) strain. We established SAMP8 mouse models to examine the consequences of noise exposure on the microbiome-gut-brain axis. Hippocampal amyloid-β (Aβ) assessment and the Morris water maze were used to evaluate AD-like changes, 16S ribosomal RNA sequencing analyses were used for intestinal flora measurements, and assessment of endothelial tight junctions and serum neurotransmitter and inflammatory mediator levels, as well as fecal microbiota transplant, was conducted to explore the underlying pathological mechanisms.

Results: Chronic noise exposure led to cognitive impairment and Aβ accumulation in young SAMP8 mice, similar to that observed in aging SAMP8 mice. Noise exposure was also associated with decreased gut microbiota diversity and compositional alterations. Axis-series studies showed that endothelial tight junction proteins were decreased in both the intestine and brain, whereas serum neurotransmitter and inflammatory mediator levels were elevated in young SAMP8 mice exposed to chronic noise, similar to the observations made in the aging group. The importance of intestinal bacteria in noise exposure-induced epithelial integrity impairment and Aβ accumulation was further confirmed through microbiota transplantation experiments. Moreover, the effects of chronic noise were generally intensity-dependent.

Conclusion: Chronic noise exposure altered the gut microbiota, accelerated age-related neurochemical and inflammatory dysregulation, and facilitated AD-like changes in the brain of SAMP8 mice.

Keywords: Alzheimer’s disease (AD); Inflammation; Microbiome-gut-brain axis; Noise; SAMP8 mouse.

Conflict of interest statement

Ethics approval

Animal treatment, husbandry, and the experimental protocols in this study were approved by the Institutional Animal Use and Care Committee of the Tianjin Institute of Environmental and Occupational Medicine.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Chronic noise-induced Alzheimer’s disease-like cognitive and pathological alterations in SAMP8 mice. a Representative traces of SAMP8 mouse paths during the training phase and probe trial. b Effect of noise exposure on escape latency in the training phase (n = 10). c Effect of noise exposure on performance in the probe trial (n = 10). d Western blot analysis (left) and quantification (right) of Aβ in the hippocampus in each group. GAPDH was used as a loading control. Data are presented as the percent change relative to the control samples (n = 6). Data are shown as the mean ± standard deviation. HN high-intensity noise exposure, LN low-intensity noise exposure
Fig. 2
Fig. 2
Summary of the gut microbial communities in each group. a Alpha diversity of the microbial community in each group analyzed by the Shannon diversity index (n = 5). b Intragroup β-diversity of the microbial community in each group measured by weighted UniFrac distance (n = 5). c Plots of weighted UniFrac-based PCoA in each group. d Relative abundances of predominant bacteria at the phylum level in each group (n = 5). HN high-intensity noise exposure, LN low-intensity noise exposure
Fig. 3
Fig. 3
Characteristics of gut microbiota composition after chronic noise exposure. a The enriched taxa in the cecal microbiota of mice are represented in cladograms. The central point represents the root of the tree (bacteria), and each ring represents the next lower taxonomic level (phylum to genus). The diameter of each circle represents the relative abundance of the taxon (n = 5). b The most differentially abundant taxa in each group identified by LDA scores generated from the LEfSe analysis (n = 5). c Comparison of the relative abundances of the dominant phyla in all groups. d Ratio of Firmicutes to Bacteroidetes in each group. e Comparison of relative abundances at the bacterial genus level in all groups. *p < 0.05, Mann-Whitney U test. HN high-intensity noise exposure, LN low-intensity noise exposure
Fig. 4
Fig. 4
Chronic noise exposure and aging diminish intestinal and brain endothelial tight junction protein expression in SAMP8 mice. a mRNA expression levels of the tight junction components in SAMP8 mouse intestine samples (n = 6). b Protein expression levels of the main tight junction components in SAMP8 mouse intestine samples (n = 4). c Protein expression levels of the main tight junction proteins in the hippocampus of SAMP8 mice (n = 4). GAPDH was used as a loading control. Data are shown as the mean ± standard deviation. HN high-intensity noise exposure, LN low-intensity noise exposure
Fig. 5
Fig. 5
Chronic noise exposure produces abnormalities in serum neurotransmitters and chemokines in SAMP8 mice. ac Enzyme-linked immunosorbent assay analysis of GABA, 5-HT, and endotoxin (ET) concentrations for each group (n = 6). d Heatmap showing the expression values of 40 serum cytokines measured by protein array (n = 4). e Normalized net intensities of cytokines showing significant intergroup changes in the protein array (n = 4). Data are shown as the mean ± standard deviation. HN high-intensity noise exposure, LN low-intensity noise exposure
Fig. 6
Fig. 6
Effect of microbiota transplant on epithelial integrity and Aβ accumulation. a Western blot analysis (left) and quantification (right) of the main tight junction components in the intestine and hippocampus of control- and HN-microbiota recipient SAMP8 mice (n = 6). b Western blot analysis (left) and quantification (right) of Aβ in the hippocampus of control- and HN-microbiota recipient SAMP8 mice (n = 6). GAPDH was used as a loading control. Data are shown as the mean ± standard deviation. HN high-intensity noise exposure, LN low-intensity noise exposure
Fig. 7
Fig. 7
Relationships among noise exposure, aging, and the microbiome-gut-brain axis. a Redundancy analysis of the relationships among the main bacterial genera, noise intensity (sound pressure level, SPL), age, and levels of endotoxin (ET) and GABA. b Bacterial taxa in genera correlated with cognitive performance and levels of ET, GABA, or 5-HT in SAMP8 mice. The heatmap shows correlation coefficients generated from a Spearman correlation analysis. *p < 0.05 and **p < 0.01. HN high-intensity noise exposure, LN low-intensity noise exposure

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