Department of Physiology, Medical College of Jiaxing University, Jiaxing, Zhejiang 314000, China; Department of Physiology, Medical College of Shihezi University, Shihezi, Xinjiang 832000, China; The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Medical College of Shihezi University, Shihezi 832000, Xinjiang, China.
Department of Physiology, Medical College of Jiaxing University, Jiaxing, Zhejiang 314000, China; Department of Physiology, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310051, China.
Sci Total Environ. 2024 Nov 20;952:175879. doi: 10.1016/j.scitotenv.2024.175879. Epub 2024 Sep 2.
There is an association between noise exposure and cognitive impairment, and noise may have a more severe impact on patients with Alzheimer's disease (AD) and mild cognitive impairment; however, the mechanisms need further investigation. This study used the classic AD animal model APP/PS1 mice to simulate the AD population, and C57BL/6J mice to simulate the normal population. We compared their cognitive abilities after noise exposure, analyzed changes in Cluster of Differentiation (CD) between the two types of mice using transcriptomics, identified the differential CD molecule: CD36 in APP/PS1 after noise exposure, and used its pharmacological inhibitor to intervene to explore the mechanism by which CD36 affects APP/PS1 cognitive abilities. Our study shows that noise exposure has a more severe impact on the cognitive abilities of APP/PS1 mice, and that the expression trends of differentiation cluster molecules differ significantly between C57BL/6J and APP/PS1 mice. Transcriptomic analysis showed that the expression of CD36 in the hippocampus of APP/PS1 mice increased by 2.45-fold after noise exposure (p < 0.001). Meanwhile, Western Blot results from the hippocampus and entorhinal cortex indicated that CD36 protein levels increased by approximately 1.5-fold (p < 0.001) and 1.3-fold (p < 0.05) respectively, after noise exposure in APP/PS1 mice. The changes in CD36 expression elevated oxidative stress levels in the hippocampus and entorhinal cortex, leading to a decrease in PI3K/AKT phosphorylation, which in turn increased M1-type microglia and A1-type astrocytes while reducing the numbers of M2-type microglia and A2-type astrocytes. This increased neuroinflammation in the hippocampus and entorhinal cortex, causing synaptic and neuronal damage in APP/PS1 mice, ultimately exacerbating cognitive impairment. These findings may provide new insights into the relationship between noise exposure and cognitive impairment, especially given the different expression trends of CD molecules in the two types of mice, which warrants further research.
噪音暴露与认知障碍之间存在关联，噪音可能对阿尔茨海默病（AD）和轻度认知障碍患者产生更严重的影响；然而，其机制仍需进一步研究。本研究使用经典的 AD 动物模型 APP/PS1 小鼠模拟 AD 人群，C57BL/6J 小鼠模拟正常人群。我们比较了它们在噪音暴露后的认知能力，通过转录组学分析了两种类型小鼠之间分化簇（CD）的变化，鉴定出差异表达的 CD 分子：APP/PS1 中的 CD36，并用其药理学抑制剂进行干预，以探索 CD36 影响 APP/PS1 认知能力的机制。我们的研究表明，噪音暴露对 APP/PS1 小鼠的认知能力有更严重的影响，并且 C57BL/6J 和 APP/PS1 小鼠之间分化簇分子的表达趋势差异显著。转录组学分析显示，APP/PS1 小鼠在噪音暴露后，其海马体中的 CD36 表达增加了 2.45 倍（p<0.001）。同时，来自海马体和内嗅皮层的 Western Blot 结果表明，CD36 蛋白水平分别增加了约 1.5 倍（p<0.001）和 1.3 倍（p<0.05）。CD36 表达的变化导致海马体和内嗅皮层的氧化应激水平升高，从而降低了 PI3K/AKT 的磷酸化水平，进而增加了 M1 型小胶质细胞和 A1 型星形胶质细胞的数量，减少了 M2 型小胶质细胞和 A2 型星形胶质细胞的数量。这种海马体和内嗅皮层的神经炎症增加导致 APP/PS1 小鼠的突触和神经元损伤，最终导致认知障碍恶化。这些发现可能为噪音暴露与认知障碍之间的关系提供新的见解，特别是考虑到两种类型小鼠的 CD 分子表达趋势不同，这值得进一步研究。
