Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
J Alzheimers Dis. 2021;82(1):307-316. doi: 10.3233/JAD-201577.
Air pollution is widely associated with accelerated cognitive decline at later ages and risk of Alzheimer's disease (AD). Correspondingly, rodent models demonstrate the neurotoxicity of ambient air pollution and its components. Our studies with nano-sized particulate matter (nPM) from urban Los Angeles collected since 2009 have shown pro-amyloidogenic and pro-inflammatory responses. However, recent batches of nPM have diminished induction of the glutamate receptor GluA1 subunit, Iba1, TNFα, Aβ42 peptide, and white matter damage. The same methods, materials, and mouse genotypes were used throughout.
Expand the nPM batch comparisons and evaluate archived brain samples to identify the earliest change in nPM potency.
Batches of nPM were analyzed by in vitro cell assays for NF-κB and Nrf2 induction for comparison with in vivo responses of mouse brain regions from mice exposed to these batches, analyzed by PCR and western blot.
Five older nPM batches (2009-2017) and four recent nPM batches (2018, 2019) for NF-κB and Nrf2 induction showed declines in nPM potency after 2017 that paralleled declines of in vivo activity from independent exposures in different years.
Transcription-based in vitro assays of nPM corresponded to the loss of in vivo potency for inflammatory and oxidative responses. These recent decreases of nPM neurotoxicity give a rationale for evaluating possible benefits to the risk of dementia and stroke in Los Angeles populations.
空气污染与晚年认知能力加速下降和阿尔茨海默病（AD）风险密切相关。相应地，啮齿动物模型显示了环境空气污染及其成分的神经毒性。我们使用自 2009 年以来收集的来自洛杉矶市区的纳米级颗粒物（nPM）进行的研究表明，其具有促淀粉样蛋白形成和促炎反应。然而，最近几批 nPM 减少了谷氨酸受体 GluA1 亚基、Iba1、TNFα、Aβ42 肽的诱导以及白质损伤。整个过程使用了相同的方法、材料和小鼠基因型。
扩展 nPM 批次比较并评估存档的脑组织样本，以确定 nPM 效力最早的变化。
通过体外细胞测定分析 nPM 批次，以比较 NF-κB 和 Nrf2 诱导，与这些批次暴露的小鼠大脑区域的体内反应进行比较，通过 PCR 和 Western blot 进行分析。
五个较旧的 nPM 批次（2009-2017 年）和四个较新的 nPM 批次（2018 年、2019 年）用于 NF-κB 和 Nrf2 诱导，在 2017 年后显示出 nPM 效力下降，与不同年份独立暴露的体内活性下降平行。
基于转录的 nPM 体外测定与体内炎症和氧化反应效力的丧失相对应。这些最近 nPM 神经毒性的降低为评估洛杉矶人群痴呆和中风风险降低的可能益处提供了依据。
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