Zeng Hui-Xian, Qin Shuang-Jian, Wu Qi-Zhen, Zeng Qing-Guo, Li Jia-Hui, Oudin Anna, Kanninen Katja M, Yang Mo, Jalava Pasi, Dong Guang-Hui, Zeng Xiao-Wen
Joint International Research Laboratory of Environment and Health, Ministry of Education, Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
J Hazard Mater. 2025 Feb 15;484:136719. doi: 10.1016/j.jhazmat.2024.136719. Epub 2024 Nov 29.
Airborne ultrafine particulate matter (PM) can enter the brain, induce microglia activation, and promote the development of Alzheimer's disease (AD). Circular RNAs (circRNAs) are also involved in AD pathogenesis. However, the role of AD-related circRNAs in PM-induced microglia activation remains unclear. Therefore, we explore cytotoxicity, microglia activation, and AD-associated circRNA expression in human microglial HMC3 cells treated with PM, and further examined circRNA expression in mice and cognitively impaired individuals. The results revealed that PM exposure decreased cell viability, increased lactate dehydrogenase activity, caused microglia activation, elevated microglial M1 maker expression, downregulated microglial M2 maker expression, and reduced AD-related circ_0061183 expression in vitro. Functionally, circ_0061183 silencing enhanced microglia activation and microglial M1 polarization, but inhibited microglial M2 polarization. Mechanistically, circ_0061183 can bind to miR-98-5p to co-regulate M2 microglial-related IL10 expression, which may affect transforming growth factor-β signaling to regulate PM-inhibited microglial M2 polarization. Moreover, circ_0061183 downregulation was observed in the brain of PM-exposed mice and AD mice and in the blood of cognitively impaired individuals. Furthermore, circ_0061183 was positively related to mini-mental state examination scores and amyloid-β42 peptide expression in elderly individuals. Overall, the current work offers epigenetic insights into the regulatory mechanisms of circRNAs on microglial activation caused by environmental pollutants.
空气中的超细颗粒物（PM）可进入大脑，诱导小胶质细胞活化，并促进阿尔茨海默病（AD）的发展。环状RNA（circRNA）也参与AD的发病机制。然而，AD相关circRNA在PM诱导的小胶质细胞活化中的作用仍不清楚。因此，我们探讨了用PM处理的人小胶质细胞HMC3中的细胞毒性、小胶质细胞活化和AD相关circRNA表达，并进一步检测了小鼠和认知障碍个体中的circRNA表达。结果显示，体外暴露于PM会降低细胞活力，增加乳酸脱氢酶活性，导致小胶质细胞活化，提高小胶质细胞M1标志物表达，下调小胶质细胞M2标志物表达，并降低AD相关circ_0061183的表达。在功能上，circ_0061183沉默增强了小胶质细胞活化和小胶质细胞M1极化，但抑制了小胶质细胞M2极化。机制上，circ_0061183可与miR-98-5p结合以共同调节M2小胶质细胞相关的IL10表达，这可能影响转化生长因子-β信号传导以调节PM抑制的小胶质细胞M2极化。此外，在暴露于PM的小鼠和AD小鼠的大脑以及认知障碍个体的血液中观察到circ_0061183下调。此外，circ_0061183与老年人的简易精神状态检查评分和淀粉样β42肽表达呈正相关。总体而言，目前的工作为circRNA对环境污染物引起的小胶质细胞活化的调控机制提供了表观遗传学见解。
