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

Li, Wenlong; Su, Donghong; Zhai, Qingfeng; Chi, Huimin; She, Xiaojun; Gao, Xiujie; Wang, Kun; Yang, Honglian; Wang, Rui; Cui, Bo

doi:10.1016/j.envres.2019.108537

Cited by 18 publications

(11 citation statements)

References 46 publications

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“…Although much is to be explored about the underlying mechanisms in Alzheimer’s disease, several animal studies have shown chronic exposure to noise to exacerbate age related changes and activate the formation of key role genes that potentially act as mediators for pathological changes related to Alzheimer’s disease in the hippocampus of mice. 56 57 58 59 Because Parkinson’ disease related dementia shares similar pathology to Alzheimer’s disease (eg, accumulation of amyloid β plaques and formation of tau hyperphosphorylation in the brain), and both diseases can often coexist, 60 we expected compatible results for both Alzheimer’s disease and Parkinson’s disease related dementia. Nevertheless, results were not so consistent, especially for railway noise.…”

Section: Discussionmentioning

confidence: 96%

Residential exposure to transportation noise in Denmark and incidence of dementia: national cohort study

Cantuaria

Waldorff

Wermuth

et al. 2021

BMJ

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Objective To investigate the association between long term residential exposure to road traffic and railway noise and risk of incident dementia. Design Nationwide prospective register based cohort study. Setting Denmark. Participants 1 938 994 adults aged ≥60 years living in Denmark between 1 January 2004 and 31 December 2017. Main outcome measures Incident cases of all cause dementia and dementia subtypes (Alzheimer’s disease, vascular dementia, and Parkinson’s disease related dementia), identified from national hospital and prescription registries. Results The study population included 103 500 participants with incident dementia, and of those, 31 219 received a diagnosis of Alzheimer’s disease, 8664 of vascular dementia, and 2192 of Parkinson’s disease related dementia. Using Cox regression models, 10 year mean exposure to road traffic and railway noise at the most (L den max) and least (L den min) exposed façades of buildings were associated with a higher risk of all cause dementia. These associations showed a general pattern of higher hazard ratios with higher noise exposure, but with a levelling off or even small declines in risk at higher noise levels. In subtype analyses, both road traffic noise and railway noise were associated with a higher risk of Alzheimer’s disease, with hazard ratios of 1.16 (95% confidence interval 1.11 to 1.22) for road L den max ≥65 dB compared with <45 dB, 1.27 (1.22 to 1.34) for road L den min ≥55 dB compared with <40 dB, 1.16 (1.10 to 1.23) for railway L den max ≥60 dB compared with <40 dB, and 1.24 (1.17 to 1.30) for railway L den min ≥50 dB compared with <40 dB. Road traffic, but not railway, noise was associated with an increased risk of vascular dementia. Results indicated associations between road traffic L den min and Parkinson’s disease related dementia. Conclusions This nationwide cohort study found transportation noise to be associated with a higher risk of all cause dementia and dementia subtypes, especially Alzheimer’s disease.

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Section: Discussionmentioning

confidence: 96%

Residential exposure to transportation noise in Denmark and incidence of dementia: national cohort study

Cantuaria

Waldorff

Wermuth

et al. 2021

BMJ

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“…With respect to ApoE4 , mTORC1 activates pathways that promote synaptogenesis and neuronal development, which would benefit cognition during youth at the expense of decreased autophagy and increased risk of accumulating mitochondrial damage and neurotoxic protein aggregates over time, as in the case of ApoE4 ( Wright et al, 2003 ; Mondadori et al, 2007 ). Indeed, the ApoE4 genotype is associated with elevated mTOR signaling ( Li et al, 2019b ). APN has been shown to induce oxidative stress in an mTORC1-dependent manner by modulating both insulin and AMPK signaling ( Fujimoto et al, 2010 ; Figure 1 ).…”

Section: Antagonistic Pleiotropymentioning

confidence: 99%

mTOR Mysteries: Nuances and Questions About the Mechanistic Target of Rapamycin in Neurodegeneration

Norwitz

Querfurth

2020

Front. Neurosci.

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The mechanistic target of rapamycin protein complex, mTORC1, has received attention in recent years for its role in aging and neurodegenerative diseases, such as Alzheimer’s disease. Numerous excellent reviews have been written on the pathways and drug targeting of this keystone regulator of metabolism. However, none have specifically highlighted several important nuances of mTOR regulation as relates to neurodegeneration. Herein, we focus on six such nuances/open questions: (1) “Antagonistic pleiotropy” – Should we weigh the beneficial anabolic functions of mTORC1 against its harmful inhibition of autophagy? (2) “Early/late-stage specificity” – Does the relative importance of these neuroprotective/neurotoxic actions change as a disease progresses? (3) “Regional specificity” – Does mTOR signaling respond differently to the same interventions in different brain regions? (4) “Disease specificity” – Could the same intervention to inhibit mTORC1 help in one disease and cause harm in another disease? (5) “Personalized therapy” – Might genetically-informed personalized therapies that inhibit particular nodes in the mTORC1 regulatory network be more effective than generalized therapies? (6) “Lifestyle interventions” – Could specific diets, micronutrients, or exercise alter mTORC1 signaling to prevent or improve the progression neurodegenerative diseases? This manuscript is devoted to discussing recent research findings that offer insights into these gaps in the literature, with the aim of inspiring further inquiry.

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“…Real-time PCR was performed as previously described [14]. Colon tissue from the exposure and control group were homogenized using a rapidly oscillating masher.…”

Section: Determination Of Gene Expression By Real-time Pcrmentioning

confidence: 99%

“…Furthermore, our recent study showed that environmental noise alone or in combination with ApoE4, one of the most important internal risk factors for sporadic late-onset AD, can aggravate the occurrence and development of AD [14]. This indicates that the combined effects of environmental noise and genetic risk factors may have a greater impact on EOAD progression than exposure to individual factors alone.…”

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confidence: 99%

Noise exposure-induced intestinal flora dysbiosis disrupts homeostasis of oxi-inflamm-barrier in the gut–brain axis of APP/PS1 mice: implications for early onset Alzheimer's disease

Cui¹,

Chi²,

Cao³

et al. 2020

Preprint

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Background: Environmental noise exposure and genetic risk factors are thought to be 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: We established APP/PS1 Tg and C57BL/6 (wild type [WT]) mouse models to evaluate the molecular pathways underlying EOAD pathophysiology following environmental noise exposure. 16S rRNA sequencing analyses were used for intestinal flora measurements and Tax4Fun were used to predict the metagenome content from 16S rRNA sequencing results; and assessment of the flora dysbiosis-triggered dyshomeostasis of oxi-inflamm-barrier and the effects of the CNS end of the gut–brain axis were conducted to explore the underlying pathological mechanisms. Results: Both WT and APP/PS1 mice showed 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 after noise exposure. Mechanistically, axis-series experiments demonstrated that after noise exposure, intestinal and hippocampal tight junction proteins levels reduced, whereas serum levels of inflammatory mediator were elevated. With regard to 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. Conclusions: 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.

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

Cited by 18 publications

References 46 publications

Residential exposure to transportation noise in Denmark and incidence of dementia: national cohort study

Residential exposure to transportation noise in Denmark and incidence of dementia: national cohort study

mTOR Mysteries: Nuances and Questions About the Mechanistic Target of Rapamycin in Neurodegeneration

Noise exposure-induced intestinal flora dysbiosis disrupts homeostasis of oxi-inflamm-barrier in the gut–brain axis of APP/PS1 mice: implications for early onset Alzheimer's disease

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