Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
Institute of Environmental and Occupational Health Sciences, College of Public Health, National Taiwan University, Room 720, No. 17, Xuzhou Rd, Taipei, 100, Taiwan.
Part Fibre Toxicol. 2022 Jun 30;19(1):44. doi: 10.1186/s12989-022-00485-8.
Air pollution, especially fine particulate matter (PM), can cause brain damage, cognitive decline, and an increased risk of neurodegenerative disease, especially alzheimer's disease (AD). Typical pathological findings of amyloid and tau protein accumulation have been detected in the brain after exposure in animal studies. However, these observations were based on high levels of PM exposure, which were far from the WHO guidelines and those present in our environment. In addition, white matter involvement by air pollution has been less reported. Thus, this experiment was designed to simulate the true human world and to discuss the possible white matter pathology caused by air pollution.
6 month-old female 3xTg-AD mice were divided into exposure and control groups and housed in the Taipei Air Pollutant Exposure System (TAPES) for 5 months. The mice were subjected to the Morris water maze test after exposure and were then sacrificed with brain dissection for further analyses. The mean mass concentration of PM during the exposure period was 13.85 μg/m. After exposure, there was no difference in spatial learning function between the two groups, but there was significant decay of memory in the exposure group. Significantly decreased total brain volume and more neuronal death in the cerebral and entorhinal cortex and demyelination of the corpus callosum were noted by histopathological staining after exposure. However, there was no difference in the accumulation of amyloid or tau on immunohistochemistry staining. For the protein analysis, amyloid was detected at significantly higher levels in the cerebral cortex, with lower expression of myelin basic protein in the white matter. A diffuse tensor image study also revealed insults in multiple white matter tracts, including the optic tract.
In conclusion, this pilot study showed that even chronic exposure to low PM concentrations still caused brain damage, such as gross brain atrophy, cortical neuron damage, and multiple white matter tract damage. Typical amyloid cascade pathology did not appear prominently in the vulnerable brain region after exposure. These findings imply that multiple pathogenic pathways induce brain injury by air pollution, and the optic nerve may be another direct invasion route in addition to olfactory nerve.
空气污染，尤其是细颗粒物（PM），可导致脑损伤、认知能力下降以及神经退行性疾病风险增加，尤其是阿尔茨海默病（AD）。动物研究中发现，在暴露后大脑中可检测到淀粉样蛋白和tau 蛋白积累的典型病理发现。然而，这些观察结果基于高水平的 PM 暴露，这远远超出了世界卫生组织的指导原则和我们环境中的 PM 暴露水平。此外，空气污染对脑白质的影响较少被报道。因此，本实验旨在模拟真实的人类世界，并探讨空气污染可能导致的脑白质病理学。
将 6 月龄雌性 3xTg-AD 小鼠分为暴露组和对照组，并在台北空气污染物暴露系统（TAPES）中饲养 5 个月。暴露后，对小鼠进行 Morris 水迷宫测试，然后进行大脑解剖以进行进一步分析。暴露期间 PM 的平均质量浓度为 13.85μg/m。暴露后，两组间空间学习功能无差异，但暴露组记忆明显衰退。暴露后组织病理学染色显示，总脑体积明显减小，大脑和海马皮质神经元死亡增加，胼胝体脱髓鞘。然而，免疫组织化学染色未见淀粉样蛋白或 tau 积累的差异。对于蛋白质分析，大脑皮质中检测到的淀粉样蛋白水平显著升高，而白质中的髓鞘碱性蛋白表达水平降低。弥散张量成像研究还显示，多个白质束包括视神经受到损伤。
总之，这项初步研究表明，即使是慢性暴露于低浓度的 PM 仍可导致脑损伤，如大脑整体萎缩、皮质神经元损伤和多个白质束损伤。暴露后，脆弱脑区并未明显出现典型的淀粉样蛋白级联病理。这些发现表明，空气污染可通过多种致病途径导致脑损伤，视神经可能是嗅神经以外的另一个直接入侵途径。
