Institute of Environmental and Occupational Health Sciences, College of Public Health, National Taiwan University, Taipei, Taiwan.
Institute of Environmental and Occupational Health Sciences, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Public Health, National Taiwan University, Taipei, Taiwan.
Sci Total Environ. 2022 Sep 10;838(Pt 4):156456. doi: 10.1016/j.scitotenv.2022.156456. Epub 2022 Jun 2.
Fine particulate matter (PM) poses a significant risk to human health. The molecular mechanisms underlying low-level PM-induced neurotoxicity in the central nervous system remain unclear. In addition, changes in lipids in response to PM exposure have not yet been fully elucidated. In this study, 3xTg-Alzheimer's disease (AD) mice experienced continuous whole-body exposure to non-concentrated PM for three consecutive months, while control mice inhaled particulate matter-filtered air over the same time span. A liquid chromatography-mass spectrometry-based lipidomic platform was used to determine the distinct lipid profiles of various brain regions. The average PM concentration during the exposure was 11.38 μg/m, which was close to the regulation limits of USA and Taiwan. The partial least squares discriminant analysis model showed distinct lipid profiles in the cortex, hippocampus, and olfactory bulb, but not the cerebellum, of mice in the exposure group. Increased levels of fatty acyls, glycerolipids, and sterol lipids, as well as the decreased levels of glycerophospholipids and sphingolipids in PM-exposed mouse brains may be responsible for the increased energy demand, membrane conformation, neuronal loss, antioxidation, myelin function, and cellular signaling pathways associated with AD development. Our research suggests that subchronic exposure to low levels of PM may cause neurotoxicity by changing the lipid profiles in a susceptible model. Lipidomics is a powerful tool to study the early effects of PM-induced AD toxicity.
细颗粒物 (PM) 对人类健康构成重大威胁。低水平 PM 诱导中枢神经系统神经毒性的分子机制仍不清楚。此外，针对 PM 暴露引起的脂质变化尚未得到充分阐明。在这项研究中，3xTg-阿尔茨海默病 (AD) 小鼠经历了连续三个月的全身非浓缩 PM 暴露，而对照小鼠在同一时间段内吸入了经过颗粒物质过滤的空气。使用基于液相色谱-质谱的脂质组学平台来确定各种大脑区域的独特脂质图谱。暴露期间的平均 PM 浓度为 11.38 μg/m，接近美国和台湾的规定限值。偏最小二乘判别分析模型显示，暴露组小鼠的大脑皮层、海马体和嗅球的脂质图谱存在明显差异，但小脑则没有。PM 暴露后，小鼠大脑中的脂肪酸、甘油脂质和甾醇脂质水平升高，而甘油磷脂和鞘脂水平降低，这可能与 AD 发展相关的能量需求增加、膜构象改变、神经元丧失、抗氧化、髓鞘功能和细胞信号通路有关。我们的研究表明，亚慢性低水平 PM 暴露可能通过改变易感模型中的脂质图谱引起神经毒性。脂质组学是研究 PM 诱导的 AD 毒性早期影响的有力工具。
