Huimin Chi1, Qingfeng Zhai1, Ming Zhang2, Donghong Su3, Wa Cao3, Wenlong Li1, Xiaojun She3, Honglian Yang3, Kun Wang3, Xiujie Gao3, Kefeng Ma3, Bo Cui3, Yugang Qiu1.
Abstract
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-β (Aβ), 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 Aβ 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 kinaseB)-GSK3β (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-GSK3β-VDAC1 signaling pathway. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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-β (Aβ), 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 Aβ 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 kinaseB)-GSK3β (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-GSK3β-VDAC1 signaling pathway. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Entities:
Keywords:
AD-like neuropathology; APP/PS1; Chronic noise; Gene–environment interaction; Synergistic effect
Year: 2021
PMID： 33761858 DOI： 10.2174/1567205018666210324114153
Source DB: PubMed Journal: Curr Alzheimer Res ISSN： 1567-2050 Impact factor: 3.498