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

Author(s): Huimin Chi, Qingfeng Zhai, Ming Zhang, Donghong Su, Wa Cao, Wenlong Li, Xiaojun She, Honglian Yang, Kun Wang, Xiujie Gao, Kefeng Ma, Bo Cui*, Yugang Qiu*

Journal Name: Current Alzheimer Research

Volume 18 , Issue 1 , 2021

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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 kinase B)-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.

Keywords: APP/PS1, chronic noise, AD-like neuropathology, synergistic effect, gene-environment interaction, Alzheimer's disease.

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Article Details

Year: 2021
Published on: 24 March, 2021
Page: [14 - 24]
Pages: 11
DOI: 10.2174/1567205018666210324114153
Price: $65

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