Airborne ultrafine particulate matter (PM0.1) 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 PM0.1-induced microglia activation remains unclear. Therefore, we explore cytotoxicity, microglia activation, and AD-associated circRNA expression in human microglial HMC3 cells treated with PM0.1, and further examined circRNA expression in mice and cognitively impaired individuals. The results revealed that PM0.1 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 PM0.1-inhibited microglial M2 polarization. Moreover, circ_0061183 downregulation was observed in the brain of PM2.5-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.

中文翻译：

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环状 RNA circ_0061183通过海绵 miR-98-5p 调节 HMC3 细胞中空气中超细颗粒诱导的小胶质细胞极化


空气中的超细颗粒物 （PM0.1） 可以进入大脑，诱导小胶质细胞激活，促进阿尔茨海默病 （AD） 的发展。环状 RNA （circRNA） 也参与 AD 发病机制。然而，AD 相关 circRNAs 在 PM0.1 诱导的小胶质细胞激活中的作用仍不清楚。因此，我们探讨了用 PM0.1 处理的人小胶质细胞 HMC3 细胞中的细胞毒性、小胶质细胞活化和 AD 相关 circRNA 表达，并进一步检查了小鼠和认知障碍个体中的 circRNA 表达。结果显示，PM0.1 暴露降低了细胞活力，增加了乳酸脱氢酶活性，导致小胶质细胞活化，提高了小胶质细胞 M1 制造商的表达，下调了小胶质细胞 M2 制造商的表达，并降低了体外 AD 相关 circ_0061183 的表达。从功能上讲，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。从机制上讲，circ_0061183 可以与 miR-98-5p 结合以共同调节 M2 小胶质细胞相关 IL10 表达，这可能会影响转化生长因子β信号传导以调节 PM0.1 抑制的小胶质细胞 M2 极化。此外，在 PM2.5 暴露小鼠和 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蛋白-β 42 肽表达呈正相关。总体而言，目前的工作为 circRNAs 对环境污染物引起的小胶质细胞活化的调节机制提供了表观遗传学见解。