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.

背景：环境风险因素，包括环境噪音应激和遗传因素，与阿尔茨海默病（AD）的发生和发展有关。然而，环境噪声与 APP/PS1 基因之间的环境-基因相互作用诱导的 AD 样病理的确切作用和机制仍不清楚。

方法：在此，我们研究了慢性噪声暴露对 APP/PS1 转基因小鼠的 AD 样神经病理学的影响。进行莫里斯水迷宫 (MWM) 任务来评估类似 AD 的变化。评估海马磷酸化 Tau、β 淀粉样蛋白 (Aβ) 和神经炎症。我们还评估了电压依赖性阴离子通道 1 (VDAC1) 正反馈环路信号的变化，以探索将 AD 样神经病理学与噪声 APP/PS1 相互作用联系起来的潜在潜在机制。

结果：长期噪声暴露显着增加了 MWM 任务中的逃避潜伏期和平台穿越次数。APP/PS1 小鼠海马中 Aβ 过量产生，伴随着 Ser396 和 Thr231 Tau 磷酸化的增加以及小胶质细胞和星形胶质细胞标记物表达的增加。此外，噪声暴露后APP/PS1小鼠海马中的VDAC1-AKT（蛋白激酶B）-GSK3β（糖原合酶激酶3β）-VDAC1信号通路异常激活。

结论：慢性噪声暴露和 APP/PS1 过度表达可能协同加剧 AD 中发生的认知障碍和神经病理变化。这种相互作用可能是由 VDAC1-AKT-GSK3β-VDAC1 信号通路的正反馈环介导的。