Circadian disturbances by altering the light-dark cycle negatively affects hematopoietic function of bone marrow in mice.

Circadian rhythms in metabolically active tissues are crucial for maintaining physical health. Circadian disturbance (CD) can cause various health issues, such as metabolic abnormalities and immune and cognitive dysfunctions. However, studies on the role of CD in immune cell development and differentiation, as well as the rhythmic expression of the core clock genes and their altered expression under CD, remain unclear. Therefore, we exposed C57bl/6j mice to repeated reversed light-dark cycles for 90 days to research the effects of CD on bone marrow (BM) hematopoietic function. We also researched the effects of CD on endogenous circadian rhythms, temporally dependent expression in peripheral blood and myeloid leukocytes, environmental homeostasis within BM, and circadian oscillations of hematopoietic-extrinsic cues. Our results confirmed that when the light and dark cycles around mice were frequently reversed, the circadian rhythmic expression of the two main circadian rhythm markers, the hypothalamic clock gene, and serum melatonin, was disturbed, indicating that the body was in a state of endogenous CD. Furthermore, CD altered the temporally dependent expression of peripheral blood and BM leukocytes and destroyed environmental homeostasis within the BM as well as circadian oscillations of hematopoietic-extrinsic cues, which may negatively affect BM hematopoiesis in mice. Collectively, these results demonstrate that circadian rhythms are vital for maintaining health and suggest that the association between CD and hematopoietic dysfunction warrants further investigation.

Early-life noise exposure causes cognitive impairment in a sex-dependent manner by disrupting homeostasis of the microbiota-gut-brain axis.

Epidemiological investigations show that noise exposure in early life is associated with health and cognitive impairment. The gut microbiome established in early life plays a crucial role in modulating developmental processes that subsequently affect brain function and behavior. Here, we examined the impact of early-life exposure to noise on cognitive function in adolescent rats by analyzing the gut microbiome and metabolome to elucidate the underlying mechanisms. Chronic noise exposure during early life led to cognitive deficits, hippocampal injury, and neuroinflammation. Early-life noise exposure showed significant difference on the composition and function of the gut microbiome throughout adolescence, subsequently causing axis-series changes in fecal short-chain fatty acid (SCFA) metabolism and serum metabolome profiles, as well as dysregulation of endothelial tight junction proteins, in both intestine and brain. We also observed sex-dependent effects of microbiota depletion on SCFA-related beneficial bacteria in adolescence. Experiments on microbiota transplantation and SCFA supplementation further confirmed the role of intestinal bacteria and related SCFAs in early-life noise-exposure-induced impairments in cognition, epithelial integrity, and neuroinflammation. Overall, these results highlight the homeostatic imbalance of microbiota-gut-brain axis as an important physiological response toward environmental noise during early life and reveals subtle differences in molecular signaling processes between male and female rats.

Lactobacillus rhamnosus GG ameliorates noise-induced cognitive deficits and systemic inflammation in rats by modulating the gut-brain axis.

Background: Environmental noise exposure is linked to neuroinflammation and imbalance of the gut microbiota. Promoting gut microbiota homeostasis may be a key factor in relieving the deleterious non-auditory effects of noise. This study aimed to investigate the effect of Lactobacillus rhamnosus GG (LGG) intervention on noise-induced cognitive deficits and systemic inflammation in rats. Methods: Learning and memory were assessed using the Morris water maze, while 16S rRNA sequencing and gas chromatography-mass spectrometry were used to analyze the gut microbiota and short-chain fatty acid (SCFA) content. Endothelial tight junction proteins and serum inflammatory mediators were assessed to explore the underlying pathological mechanisms. Results: The results indicated that Lactobacillus rhamnosus GG intervention ameliorated noise-induced memory deterioration, promoted the proliferation of beneficial bacteria, inhibited the growth of harmful bacteria, improved dysregulation of SCFA-producing bacteria, and regulated SCFA levels. Mechanistically, noise exposure led to a decrease in tight junction proteins in the gut and hippocampus and an increase in serum inflammatory mediators, which were significantly alleviated by Lactobacillus rhamnosus GG intervention. Conclusion: Taken together, Lactobacillus rhamnosus GG intervention reduced gut bacterial translocation, restored gut and blood-brain barrier functions, and improved gut bacterial balance in rats exposed to chronic noise, thereby protecting against cognitive deficits and systemic inflammation by modulating the gut-brain axis.

Around-the-Clock Noise Induces AD-like Neuropathology by Disrupting Autophagy Flux Homeostasis.

Environmental noise is a common hazard in military operations. Military service members during long operations are often exposed to around-the-clock noise and suffer massive emotional and cognitive dysfunction related to an Alzheimer's disease (AD)-like neuropathology. It is essential to clarify the mechanisms underlying the effects of around-the-clock noise exposure on the central nervous system. Here, Wistar rats were continuously exposed to white noise (95 dB during the on-duty phase [8:00-16:00] and 75 dB during the off-duty phase (16:00-8:00 the next day)) for 40 days. The levels of phosphorylated tau, amyloid-ß (Aß), and neuroinflammation in the cortex and hippocampus were assessed and autophagosome (AP) aggregation was observed by transmission electron microscopy. Dyshomeostasis of autophagic flux resulting from around-the-clock noise exposure was assessed at different stages to investigate the potential pathological mechanisms. Around-the-clock noise significantly increased Aß peptide, tau phosphorylation at Ser396 and Ser404, and neuroinflammation. Moreover, the AMPK-mTOR signaling pathway was depressed in the cortex and the hippocampus of rats exposed to around-the-clock noise. Consequently, autophagosome-lysosome fusion was deterred and resulted in AP accumulation. Our results indicate that around-the-clock noise exposure has detrimental influences on autophagic flux homeostasis and may be associated with AD-like neuropathology in the cortex and the hippocampus.

A rapid, non-invasive method for fatigue detection based on voice information.

Fatigue results from a series of physiological and psychological changes due to continuous energy consumption. It can affect the physiological states of operators, thereby reducing their labor capacity. Fatigue can also reduce efficiency and, in serious cases, cause severe accidents. In addition, it can trigger pathological-related changes. By establishing appropriate methods to closely monitor the fatigue status of personnel and relieve the fatigue on time, operation-related injuries can be reduced. Existing fatigue detection methods mostly include subjective methods, such as fatigue scales, or those involving the use of professional instruments, which are more demanding for operators and cannot detect fatigue levels in real time. Speech contains information that can be used as acoustic biomarkers to monitor physiological and psychological statuses. In this study, we constructed a fatigue model based on the method of sleep deprivation by collecting various physiological indexes, such as P300 and glucocorticoid level in saliva, as well as fatigue questionnaires filled by 15 participants under different fatigue procedures and graded the fatigue levels accordingly. We then extracted the speech features at different instances and constructed a model to match the speech features and the degree of fatigue using a machine learning algorithm. Thus, we established a method to rapidly judge the degree of fatigue based on speech. The accuracy of the judgment based on unitary voice could reach 94%, whereas that based on long speech could reach 81%. Our fatigue detection method based on acoustic information can easily and rapidly determine the fatigue levels of the participants. This method can operate in real time and is non-invasive and efficient. Moreover, it can be combined with the advantages of information technology and big data to expand its applicability.

[Effects of GLAST gene knockout on phenotype and hearing in mice].

OBJECTIVE: To investigate the effects of glutamate aspartate transporter (GLAST)deletion on the normal auditory function of mice. METHODS: We hybridized GLAST+/- mice with C57BL/6J background and identified the genotypes of their offspring by agarose gel electrophoresis. 9-10-week-old mice were selected to detect the expression of GLAST protein in the cochlea by immunofluorescence staining and to verify the knockout results(n=3). The changes in weight from 7 days to 30 days after birth and the 30-day body length of male and female mice were compared(n=8). The auditory brainstem response(ABR) was used to detect the auditory threshold and the amplitude of wave I in 9-10-week-old male and female mice(n=5). RESULTS: Male GLAST-/- mice had shown significantly lower weight and body length compared to male GLAST+/+ and GLAST+/- mice(P＜0.01), and male GLAST-/- mice showed significant differences compared to GLAST+/+ from P7 to P30 statistical time. Male GLAST-/- mice exhibited a significant reduction in weight after P15 compared to male GLAST+/- mice. In contrast, no significant differences in weight and body length were observed in female GLAST-/- mice compared with female GLAST+/+ and GLAST+/- mice. There was no difference in the hearing threshold detected by ABR between the three genotypes in both male and female mice, but the amplitude of wave I in GLAST-/- mice was significantly lower than that in male GLAST+/+ mice(P＜0.01). In contrast, the amplitude of wave I in females was reduced throughout the stimulus intensity but was most significant only at high-intensity stimulation (e.g.80 dB, 90 dB) (P＜0.05). CONCLUSION: GLAST knockout affects the normal growth and development of male mice, and decreases the amplitude of wave I, but do not change the threshold, suggesting that GLAST knockout may lead to synaptic pathological changes, and there are gender differences in this effect.

The antioxidant effect of triptolide contributes to the therapy in a collagen-induced arthritis rat model.

BACKGROUND: As a chronic autoimmune disease, rheumatoid arthritis (RA) is related to oxidative stress, which may lead to the occurrence and persistence of inflammation in RA. The purpose of this study is to evaluate the potential antioxidant effect of triptolide in collagen-induced arthritis (CIA) rat model. METHODS: We examined the severity of arthritis, levels of local and systemic oxidative stress, periarticular bone erosion and weight of organs in CIA rats treated with triptolide. RESULTS: We found that triptolide decreased the paw thickness and clinical arthritis score, significantly. The mRNA expression and activity of myeloperoxidase and inducible nitric oxide synthase were remarkably decreased in the paws of the CIA rats after triptolide treatment. Triptolide significantly inhibited the levels of nitrite and nitrate in serum, as well as the urinary level of dityrosine. Triptolide treatment also markedly increased bone volume of tibia, but suppressed epiphyseal plate thickness of both femur and tibia. In addition, there was no significant difference in the weight of organs after the therapy, except decreased spleen weight. CONCLUSIONS: These results suggested that the local and systemic oxidative stress was enhanced in the CIA rats and the therapeutic dose of triptolide had a definite antioxidant effect.

Disruption of Glutamate Release and Uptake-Related Protein Expression After Noise-Induced Synaptopathy in the Cochlea.

High-intensity noise can cause permanent hearing loss; however, short-duration medium-intensity noise only induces a temporary threshold shift (TTS) and damages synapses formed by inner hair cells (IHCs) and spiral ganglion nerves. Synaptopathy is generally thought to be caused by glutamate excitotoxicity. In this study, we investigated the expression levels of vesicle transporter protein 3 (Vglut3), responsible for the release of glutamate; glutamate/aspartate transporter protein (GLAST), responsible for the uptake of glutamate; and Na+/K+-ATPase α1 coupled with GLAST, in the process of synaptopathy in the cochlea. The results of the auditory brainstem response (ABR) and CtBP2 immunofluorescence revealed that synaptopathy was induced on day 30 after 100 dB SPL noise exposure in C57BL/6J mice. We found that GLAST and Na+/K+-ATPase α1 were co-localized in the cochlea, mainly in the stria vascularis, spiral ligament, and spiral ganglion cells. Furthermore, Vglut3, GLAST, and Na+/K+-ATPase α1 expression were disrupted after noise exposure. These results indicate that disruption of glutamate release and uptake-related protein expression may exacerbate the occurrence of synaptopathy.

Effects of noise and low-concentration carbon monoxide exposure on rat immunity.

OBJECTIVE: To evaluate the immunotoxicity and effects of noise and/or low-concentration carbon monoxide (CO) exposure on immune organs and immune functions in rats. METHODS: Male Wistar rats exposed to 98 dB(A) white noise and/or 100 ppm CO 4 h/d for 30 d were used to determine the pathological changes in the thymus and spleen, and variations in leukocyte counts, inflammatory factors, and immunoglobulin (Ig) concentrations. RESULTS: The boundaries of the cortex and medulla of the thymus were unclear following noise and combined exposure. The pathological changes in spleen after CO and combined exposure included blurred boundaries of red-pulp and white-pulp, disappearance of normal splenic nodules and neutrophil infiltration. After exposure to noise and in combination, leukocyte and lymphocyte counts decreased significantly. After exposure to low-concentration CO and in combination, serum IgM and IgG levels decreased significantly, but the levels of tumor necrosis factor-α and interferon-γ levels increased significantly. Eosinophils and IgA levels decreased significantly following exposure to noise and/or low concentration of CO, while the level of interleukin-1 increased significantly. Monocytes increased significantly only under noise or CO exposure, but not under combined exposure. CONCLUSIONS: Noise and/or low-concentration CO exposure may suppress innate and adaptive immune functions and induce inflammatory responses. Noise exposure mainly affected the innate immune function of rats, whereas low-concentration CO exposure mainly affected adaptive immune functions. Combined exposure presented higher immunotoxicity than noise or CO alone, suggesting that exposure to noise and low-concentration CO in the living and working environments can affect the immune system.

APP/PS1 Gene-Environment Noise Interaction Aggravates AD-like Neuropathology in Hippocampus Via Activation of the VDAC1 Positive Feedback Loop.

BACKGROUND: Environmental risk factors, including environmental noise stress, and genetic factors, have been associated with the occurrence and development of Alzheimer's disease (AD). However, the exact role and mechanism of AD-like pathology induced by environment-gene interactions between environmental noise and APP/PS1 gene remain elusive. METHODS: Herein, we investigated the impact of chronic noise exposure on AD-like neuropathology in APP/PS1 transgenic mice. The Morris water maze (MWM) task was conducted to evaluate AD-like changes. The hippocampal phosphorylated Tau, amyloid-ß (Aß), and neuroinflammation were assessed. We also assessed changes in positive feedback loop signaling of the voltage-dependent anion channel 1 (VDAC1) to explore the potential underlying mechanism linking AD-like neuropathology to noise-APP/PS1 interactions. RESULTS: Long-term noise exposure significantly increased the escape latency and the number of platform crossings in the MWM task. The Aß overproduction was induced in the hippocampus of APP/PS1 mice, along with the increase of Tau phosphorylation at Ser396 and Thr231 and the increase of the microglia and astrocytes markers expression. Moreover, the VDAC1-AKT (protein kinase B)-GSK3ß (glycogen synthase kinase 3 beta)-VDAC1 signaling pathway was abnormally activated in the hippocampus of APP/PS1 mice after noise exposure. CONCLUSION: Chronic noise exposure and APP/PS1 overexpression may synergistically exacerbate cognitive impairment and neuropathological changes that occur in AD. This interaction may be mediated by the positive feedback loop of the VDAC1-AKT-GSK3ß-VDAC1 signaling pathway.

Environmental noise stress disturbs commensal microbiota homeostasis and induces oxi-inflammmation and AD-like neuropathology through epithelial barrier disruption in the EOAD mouse model.

BACKGROUND: Both genetic factors and environmental hazards, including environmental noise stress, have been associated with gut microbiome that exacerbates Alzheimer's disease (AD) pathology. However, the role and mechanism of environmental risk factors in early-onset AD (EOAD) pathogenesis remain unclear. METHODS: The molecular pathways underlying EOAD pathophysiology following environmental noise exposure were evaluated using C57BL/6 wild-type (WT) and APP/PS1 Tg mouse models. The composition differences in intestinal microbiota were analyzed by 16S rRNA sequencing and Tax4Fun to predict the metagenome content from sequencing results. An assessment of the flora dysbiosis-triggered dyshomeostasis of oxi-inflamm-barrier and the effects of the CNS end of the gut-brain axis was conducted to explore the underlying pathological mechanisms. RESULTS: Both WT and APP/PS1 mice showed a statistically significant relationship between environmental noise and the taxonomic composition of the corresponding gut microbiome. Bacterial-encoded functional categories in noise-exposed WT and APP/PS1 mice included phospholipid and galactose metabolism, oxidative stress, and cell senescence. These alterations corresponded with imbalanced intestinal oxidation and anti-oxidation systems and low-grade systemic inflammation following noise exposure. Mechanistically, axis-series experiments demonstrated that following noise exposure, intestinal and hippocampal tight junction protein levels reduced, whereas serum levels of inflammatory mediator were elevated. Regarding APP/PS1 overexpression, noise-induced abnormalities in the gut-brain axis may contribute to aggravation of neuropathology in the presymptomatic stage of EOAD mice model. CONCLUSION: Our results demonstrate that noise exposure has deleterious effects on the homeostasis of oxi-inflamm-barrier in the microbiome-gut-brain axis. Therefore, at least in a genetic context, chronic noise may aggravate the progression of EOAD.

Efficient tidal channel networks alleviate the drought-induced die-off of salt marshes: Implications for coastal restoration and management.

Massive die-off in salt marshes is one of the most common examples of widespread degradation in marine and coastal ecosystems. In salt marshes, tidal channel networks facilitate the exchange of water, nutrients, sediments and biota with the open marine environments. However, quantitative analyses of the role of channel networks in alleviating vegetation die-off in salt marshes are scarce. Here we quantified the spatial-temporal development of marsh vegetation die-off in the northern Liaodong Bay by analyzing aerial images before, during, and after a drought (from 2014 to 2018). We found that Suaeda salsa marshes have recently experienced large-scale die-off. The extent of vegetation die-off increases with increasing distance from the channel network. Moreover, our results suggested that efficient tidal channel networks (high drainage density, low mean unchanneled path length) can mitigate die-off at the watershed scale. We presented possible abiotic & biotic processes in channel networks that explain this spatial dynamic. Our study highlights the importance of efficient tidal channel networks in mitigating die-off and enhancing the resistance of marshes to droughts, and call for incorporating theses dynamics in coastal restoration and management.

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

BACKGROUND: Chronic noise exposure is one environmental hazard that is associated with genetic susceptibility factors that increase Alzheimer's disease (AD) pathogenesis. However, the comprehensive understanding of the link between chronic noise stress and AD is limited. Herein, we investigated the effects of chronic noise exposure on AD-like changes in senescence-accelerated mouse prone 8 (SAMP8). METHODS: A total of 30 male SAMP8 mice were randomly divided into the noise-exposed group, the control group, and aging group (positive controls), and mice in the exposure group were exposed to 98 dB SPL white noise for 30 consecutive days. Transcriptome analysis and AD-like neuropathology of hippocampus were examined by RNA sequencing and immunoblotting. Enzyme-linked immunosorbent assay and real-time PCR were used to further determine the differential gene expression and explore the underlying mechanisms of chronic noise exposure in relation to AD at the genome level. RESULTS: Chronic noise exposure led to amyloid beta accumulation and increased the hyperphosphorylation of tau at the Ser202 and Ser404 sites in young SAMP8 mice; similar observations were noted in aging SAMP8 mice. We identified 21 protein-coding transcripts that were differentially expressed: 6 were downregulated and 15 were upregulated after chronic noise exposure; 8 genes were related to AD. qPCR results indicated that the expression of Arc, Egr1, Egr2, Fos, Nauk1, and Per2 were significantly high in the noise exposure group. These outcomes mirrored the results of the RNA sequencing data. CONCLUSIONS: These findings further revealed that chronic noise exposure exacerbated aging-like impairment in the hippocampus of the SAMP8 mice and that the protein-coding transcripts discovered in the study may be key candidate regulators involved in environment-gene interactions.

Proteomes analysis reveals the involvement of autophagy in AD-like neuropathology induced by noise exposure and ApoE4.

BACKGROUND: Noise is one of the most important environmental health hazards for humans. Environmental noise or apolipoprotein ε4 (ApoE4) can cause typical Alzheimer's disease (AD)-like pathological changes, which is characterized by progressive cognitive decline and neurodegenerative lesions. Gene-environment interactions may accelerate cognitive decline and increase AD risk. However, there is limited experimental evidence regarding the underlying mechanisms of noise-ApoE4 interactions and AD, which may be closely related to AD development. METHODS: In this study, we investigated the combined effects of chronic noise exposure and the ApoE4 gene activation on hippocampus by using proteomics and differentially expressed proteins were found through performed gene ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. In addition, we assessed the changes in adult hippocampal neurogenesis and potential underlying mechanism for AD-like neuropathology. RESULTS: Relative to control rats, combined exposure of noise and ApoE4 synergistically increased the characteristic pathological amyloid ß-protein of AD-like neuropathology changes in hippocampus. The research identifies a total of 4147 proteins and 15 differentially expressed proteins in hippocampus. Furthermore, comparison of several of the diverse key pathways studied (e.g., PI3K/AKT, insulin, calpain-CDK5, and mammalian target of rapamycin (mTOR) signaling pathways) help to articulate the different mechanisms involved in combined effects of noise and ApoE4 on AD-like pathology. We verified four selected proteins, namely, eukaryotic translation elongation factor 1 epsilon 1, glycine amidinotransferase, nucleoredoxin, and tuberous sclerosis 1 proteins. Validation data shows significant effects of chronic noise and ApoE4 on the expression of four selected proteins, eukaryotic translation elongation factor 1 epsilon 1, glycine amidinotransferase, nucleoredoxin, and tuberous sclerosis 1 proteins, and mTOR and autophagy-related proteins, which share significant interaction effect of chronic noise and ApoE4. CONCLUSION: Gene-environment interactions between chronic noise and ApoE4 activate the mTOR signaling, decrease autophagy, and facilitate AD-like changes in the hippocampus. Thus, our findings may help elucidate the role of gene-environment interactions in AD development.

Chronic noise exposure exacerbates AD-like neuropathology in SAMP8 mice in relation to Wnt signaling in the PFC and hippocampus.

Non-genetic environmental hazards are thought to be associated with genetic susceptibility factors that increase Alzheimer's disease (AD) pathogenesis. Aging and chronic noise exposure have been considered important factors in the AD. Here, we investigated the impact of chronic noise exposure on the AD-like neuropathology in the senescence-accelerated prone mouse (SAMP8) and the underlying mechanisms of such effects. We examined the consequences of AD-like neuropathology in 3-month-old SAMP8 mice using low- and high-intensity noise exposure and 8-month-old SAMP8 mice as aging positive controls. Immunoblotting and immunohistochemistry were conducted to examine AD-like pathological changes and potential mechanisms. Chronic noise exposure led to progressive overproduction of Aß and increased the hyperphosphorylation of tau at Ser396, Thr205, and Thr231 sites in the hippocampus and the prefrontal cortex (PFC) in young SAMP8 mice, similar to that observed in aging SAMP8 mice. Both noise exposure and aging could cause a significant downregulation in Wnt signaling expression. These findings demonstrate that chronic noise stress exacerbated AD-like neuropathology, possibly by disrupting Wnt signaling and triggering aberrant tau hyperphosphorylation and Aß in the PFC and hippocampus.

Effects of chronic noise exposure on the microbiome-gut-brain axis in senescence-accelerated prone mice: implications for Alzheimer's disease.

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-ß (Aß) 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 Aß 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 Aß 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.

Effects of chronic noise on the corticotropin-releasing factor system in the rat hippocampus: relevance to Alzheimer's disease-like tau hyperphosphorylation.

BACKGROUND: Chronic noise exposure has been associated with tau hyperphosphorylation and Alzheimer's disease (AD)-like pathological changes, but the underlying mechanism is unknown. In this study, we explored the effects of long-term noise exposure on the corticotropin-releasing factor (CRF) system in the hippocampus and its role in noise-induced tau phosphorylation. METHODS: Sixty-four rats were randomly divided into the noise-exposed group and the control group, and rats in the exposure group were exposed to 95 dB SPL white noise for 30 consecutive days. The levels of CRF, CRFR1, CRFR2, and total tau and phosphorylated tau (p-tau) at Ser396 (S396) and Thr205 (T205) in the hippocampus were measured at different time points after the final noise exposure. The co-localized distribution of CRF and p-tau (T205) in the hippocampus was evaluated using double-labeling immunofluorescence. RESULTS: Long-term exposure to noise for 30 consecutive days significantly increased the expression of CRF and CRFR1 and their mRNAs levels in the hippocampus, which persisted for 7 days after final exposure. In contrast, CRFR2 was raised for 3-7 days following the last exposure. These alterations were also concomitant with the phosphorylation of tau at S396 and T205. Furthermore, there was co-localization of p-tau and CRF in hippocampal neurons. CONCLUSION: Chronic noise leads to long-lasting increases in the hippocampal CRF system and the hyperphosphorylation of tau in the hippocampus. Our results also provide evidence for the involvement of the CRF system in noise-induced AD-like neurodegeneration.

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

Chronic noise exposure has been implicated in increased risk of diabetes. However, there is limited experimental evidence of the mechanisms linking chronic noise stress and glucose metabolism. We addressed this in the present study by examining glucose metabolism, immune response, and changes in gut microbiota/host inflammatory homeostasis in rats exposed to noise for 30 consecutive days. Chronic noise exposure increased blood glucose and corticosterone levels for at least 14 days after cessation of noise. Stressed rats also exhibited elevated levels of glycogen and triglyceride in the liver and impaired hepatic insulin production via insulin-induced insulin receptor/insulin receptor substrate 1/glycogen synthase kinase 3ß signalling, which persisted for 3-14 days after cessation of noise exposure. Chronic noise altered the percentage of Proteobacteria and Actinobacteria in the gut, increasing Roseburia but decreasing Faecalibacterium levels in the cecum relative to controls. Immunoglobulin A, interleukin 1ß, and tumor necrosis factor α levels were also elevated in the intestine of these animals, corresponding to noise-induced abnormalities in glucose regulation and insulin sensitivity. These results suggest that lifelong environmental noise exposure could have cumulative effects on diabetes onset and development resulting from alterations in gut microbiota composition and intestinal inflammation.

Effects of chronic noise on mRNA and protein expression of CRF family molecules and its relationship with p-tau in the rat prefrontal cortex.

Chronic noise exposure has been associated with Alzheimer's disease (AD)-like pathological changes, such as tau hyperphosphorylation and ß-amyloid peptide accumulation in the prefrontal cortex (PFC). Corticotropin-releasing factor (CRF) is the central driving force in the stress response and a regulator of tau phosphorylation via binding to CRF receptors (CRFR). Little is known about the CRF system in relation to noise-induced AD-like changes in the PFC. The aim of this study was to explore the effects of chronic noise exposure on the CRF system in the PFC of rats and its relationship to tau phosphorylation. Male Wistar rats were randomly divided into control and noise exposure groups. The CRF system was evaluated following chronic noise exposure (95dB sound pressure level white noise, 4h/day×30days). Chronic noise significantly accelerated the progressive overproduction of corticosterone and upregulated CRF and CRFR1 mRNA and protein, both of which persisted 7-14days after noise exposure. In contrast, CRFR2 was elevated 3-7days following the last stimulus. Double-labeling immunofluorescence co-localized p-tau with CRF in PFC neurons. The results suggest that chronic noise exposure elevates the expression of the CRF system, which may contribute to AD-like changes.