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

[ Vol. 18 , Issue. 1 ]

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* and Yugang Qiu*   Pages 14 - 24 ( 11 )

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 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.

Affiliation:

Weifang Medical University, Weifang, Weifang Medical University, Weifang, Tianjin Centers for Disease Control and Prevention, Tianjin, Tianjin Institute of Environmental and Operational Medicine, Tianjin, Tianjin Institute of Environmental and Operational Medicine, Tianjin, Weifang Medical University, Weifang, Tianjin Institute of Environmental and Operational Medicine, Tianjin, Tianjin Institute of Environmental and Operational Medicine, Tianjin, Tianjin Institute of Environmental and Operational Medicine, Tianjin, Tianjin Institute of Environmental and Operational Medicine, Tianjin, Tianjin Institute of Environmental and Operational Medicine, Tianjin, Tianjin Institute of Environmental and Operational Medicine, Tianjin, Weifang Medical University, Weifang



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