Zhang Bo, Wang Jiaojiao, Chen Junhong, Pan Xueli
Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang 561113, China; Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry, Guizhou Medical University, Guiyang 561113, China.
Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang 561113, China; Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry, Guizhou Medical University, Guiyang 561113, China.
Ecotoxicol Environ Saf. 2025 Jun 1;297:118251. doi: 10.1016/j.ecoenv.2025.118251. Epub 2025 Apr 27.
Health damage caused by environmental arsenic pollution has attracted widespread attention, with Alzheimer's disease (AD) thought to be one of the adverse effects of long-term arsenic exposure. In this study, we sought to investigate the relationship between arsenic exposure and AD-like neurodegeneration and to determine the role of microglia in the process of AD-like neurodegeneration induced by arsenic exposure. The relationship between arsenic exposure and AD-like neurodegeneration was investigated using cognitive assessments and biological experiments. Arsenic exposure induced memory impairment in C57BL/6 mice and resulted in a significant increase in the number of Aβ and pTau cells in the entorhinal cortex and hippocampus with neuronal granular vacuolar degeneration and necroptosis, accompanied by upregulated expression of related proteins, which showed dose- and time-response relationships. Arsenic exposure intensified memory decline in FAD mice with accelerated AD-like neurodegeneration. Correlation analysis showed a negative correlation between memory impairment and neurodegeneration in the entorhinal cortex and hippocampus in mice. Arsenic exposure also activated microglia in the entorhinal cortex and hippocampus, with enlargement of the cytosol, shortened and thickened cell protrusions, hypertrophic changes, and abnormal proliferation, as well as upregulated expression of the pro-inflammatory cytokines TNF-α and IL-1β. Arsenic exposure induced overactivation of microglia in the entorhinal cortex and hippocampus of FAD mice, resulting in de-branching or bulbous protrusions and fragmented cytoplasm. Our findings suggest that arsenic exposure promotes the occurrence and development of AD-like neurodegeneration via the activation of microglia, which induces neuroinflammation in mice.
环境砷污染造成的健康损害已引起广泛关注，阿尔茨海默病（AD）被认为是长期砷暴露的不良影响之一。在本研究中，我们试图探究砷暴露与AD样神经退行性变之间的关系，并确定小胶质细胞在砷暴露诱导的AD样神经退行性变过程中的作用。通过认知评估和生物学实验研究了砷暴露与AD样神经退行性变之间的关系。砷暴露诱导C57BL/6小鼠出现记忆障碍，并导致内嗅皮质和海马中Aβ和pTau细胞数量显著增加，伴有神经元颗粒空泡变性和坏死性凋亡，相关蛋白表达上调，呈现剂量和时间反应关系。砷暴露加剧了FAD小鼠的记忆衰退，加速了AD样神经退行性变。相关性分析显示，小鼠内嗅皮质和海马中的记忆障碍与神经退行性变呈负相关。砷暴露还激活了内嗅皮质和海马中的小胶质细胞，表现为胞质增大、细胞突起缩短变粗、肥大性改变和异常增殖，以及促炎细胞因子TNF-α和IL-1β表达上调。砷暴露诱导FAD小鼠内嗅皮质和海马中的小胶质细胞过度激活，导致分支减少或球状突起以及细胞质碎片化。我们的研究结果表明，砷暴露通过激活小胶质细胞促进AD样神经退行性变的发生和发展，进而在小鼠中诱导神经炎症。
