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.