Exposure to quasi-ultrafine particulate matter accelerates memory impairment and Alzheimer's disease-like neuropathology in the AppNL-G-F knock-in mouse model.
Exposure to quasi-ultrafine particulate matter accelerates memory impairment and Alzheimer's disease-like neuropathology in the AppNL-G-F knock-in mouse model.
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在 AppNL-G-F 敲入小鼠模型中，接触准超细颗粒物会加速记忆障碍和阿尔茨海默病样神经病理学。
DOI：
10.1093/toxsci/kfad036
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Saito,Takashi
中科院分区：
文献类型：
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作者：
Kilian,JasonG;Mejias-Ortega,Marina;Hsu,Heng-Wei;Herman,DavidA;Vidal,Janielle;Arechavala,RebeccaJ;Renusch,Samantha;Dalal,Hansal;Hasen,Irene;Ting,Amanda;Rodriguez-Ortiz,CarlosJ;Lim,Siok-Lam;Lin,Xiaomeng;Vu,Joan;Saito,Takashi
暴露于由颗粒物（PM）组成的交通相关空气污染与认知能力下降相关，导致阿尔茨海默病（AD）。在本研究中，我们试图研究暴露于超细PM的神经毒性效应，以及它如何加剧野生型（WT）小鼠和AD敲入小鼠模型的神经元丢失和AD样神经病理学（附录NL-G-F/+-KI）当暴露发生在病理前阶段或存在神经病理学的较晚年龄时。附录NL-G-F/+-KI和WT小鼠从3或9月龄开始暴露于来自加州欧文当地环境空气的浓缩超细PM 12周。暴露于颗粒物的动物接受浓缩的超细PM高达8倍以上的环境水平，而对照组动物暴露于净化空气。颗粒物暴露导致病理前AppNL-G-F/+-KI小鼠的记忆任务显著受损，而淀粉样蛋白-β病理学、突触变性和神经炎症无可测量的变化。在老年时，暴露于PM的WT和AppNL-G-F/+-KI小鼠均表现出显著的记忆障碍沿着神经元丢失。在AppNL-G-F/+-KI小鼠中，我们还检测到淀粉样蛋白-β积聚增加和潜在有害的胶质细胞活化，包括铁蛋白阳性小胶质细胞和C3阳性星形胶质细胞。这种胶质细胞的激活可能会促进大脑中退化后果的级联反应。我们的研究结果表明，暴露于PM损害认知功能，在这两个年龄段，而AD相关的病理和神经元丢失的恶化可能取决于病理阶段，老化，和/或状态的胶质细胞激活。需要进一步的研究来揭示PM暴露激活的神经胶质细胞活化的神经毒性作用。
Exposure to traffic-related air pollution consisting of particulate matter (PM) is associated with cognitive decline leading to Alzheimer’s disease (AD). In this study, we sought to examine the neurotoxic effects of exposure to ultrafine PM and how it exacerbates neuronal loss and AD-like neuropathology in wildtype (WT) mice and a knock-in mouse model of AD (AppNL-G-F/+-KI) when the exposure occurs at a prepathologic stage or at a later age with the presence of neuropathology.AppNL-G-F/+-KI and WT mice were exposed to concentrated ultrafine PM from local ambient air in Irvine, California, for 12 weeks, starting at 3 or 9 months of age. Particulate matter-exposed animals received concentrated ultrafine PM up to 8 times above the ambient levels, whereas control animals were exposed to purified air. Particulate matter exposure resulted in a marked impairment of memory tasks in prepathologicAppNL-G-F/+-KI mice without measurable changes in amyloid-β pathology, synaptic degeneration, and neuroinflammation. At aged, both WT andAppNL-G-F/+-KI mice exposed to PM showed a significant memory impairment along with neuronal loss. InAppNL-G-F/+-KI mice, we also detected an increased amyloid-β buildup and potentially harmful glial activation including ferritin-positive microglia and C3-positive astrocytes. Such glial activation could promote the cascade of degenerative consequences in the brain. Our results suggest that exposure to PM impairs cognitive function at both ages while exacerbation of AD-related pathology and neuronal loss may depend on the stage of pathology, aging, and/or state of glial activation. Further studies will be required to unveil the neurotoxic role of glial activation activated by PM exposure.