A growing body of epidemiological literature indicates that particulate matter (PM) air pollution exposure is associated with elevated Alzheimer’s disease (AD) risk and may exacerbate AD-related cognitive decline. Of concern is exposure to the ultrafine PM (UFP) fraction (≤100 nm), which deposits efficiently throughout the respiratory tract, has higher rates of translocation to secondary organs, like brain, and may induce inflammatory changes. We, therefore, hypothesize that exposure to UFPs will exacerbate cognitive deficits in a mouse model of AD. The present study assessed alterations in learning and memory behaviors in aged (12.5 months) male 3xTgAD and non-transgenic mice following a 2-week exposure (4-h/day, 4 days/week) to concentrated ambient UFPs using the Harvard ultrafine concentrated ambient particle system (HUCAPS) or filtered air. Beginning one month following exposure, locomotor activity, spatial learning and memory, short-term recognition memory, appetitive motivation, and olfactory discrimination were assessed. No effects on locomotor activity were found following HUCAPS exposure (number concentration, 1 × 104–4.7 × 105 particles/cm3; mass concentration, 29–132 μg/m3). HUCAPS-exposed mice, independent of AD background, showed a significantly decreased spatial learning, mediated through reference memory deficits, as well as short-term memory deficits in novel object recognition testing. AD mice displayed diminished spatial working memory, potentially a result of olfactory deficits, and short-term memory. AD background modulated HUCAPS-induced changes on appetitive motivation and olfactory discrimination, specifically enhancing olfactory discrimination in NTg mice. Modeling variation in appetitive motivation as a covariate in spatial learning and memory, however, did not support the conclusion that differences in motivation significantly underlie changes in spatial learning and memory. A short-term inhalation exposure of aged mice to ambient UFPs at human-relevant concentrations resulted in protracted (testing spanning 1–6.5 months post-exposure) adverse effects on multiple memory domains (reference and short-term memory) independent of AD background. Impairments in learning and memory were present when accounting for potential covariates like motivational changes and locomotor activity. These results highlight the need for further research into the potential mechanisms underlying the cognitive effects of UFP exposure in adulthood.

中文翻译：

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老年3xTgAD阿尔茨海默氏病小鼠暴露于环境超细颗粒物后的选择性记忆和行为改变。

越来越多的流行病学文献表明，空气中的颗粒物（PM）暴露与阿尔茨海默氏病（AD）风险升高有关，并可能加剧与AD相关的认知能力下降。令人关注的是暴露于超细颗粒物（UFP）部分（≤100nm），该部分有效地沉积在整个呼吸道中，易位至次要器官（如大脑）的速率更高，并可能引起炎症变化。因此，我们假设暴露于UFP会加剧AD小鼠模型中的认知缺陷。本研究评估了使用哈佛超浓缩浓缩液浓缩2周（每天4小时，每天4天）每周2次（每天4小时，每天4天）雄性3xTgAD雄性和非转基因小鼠（12.5个月）的学习和记忆行为的变化环境粒子系统（HUCAPS）或过滤后的空气。在接触后一个月开始，评估运动活动，空间学习和记忆，短期识别记忆，食欲动机和嗅觉歧视。HUCAPS暴露后未发现对运动能力的影响（数量浓度为1×104–4.7×105颗粒/ cm3；质量浓度为29–132μg/ m3）。暴露于HUCAPS的小鼠，与AD背景无关，在参考物体记忆缺陷以及新型物体识别测试中的短期记忆缺陷的介导下，空间学习明显减少。AD小鼠表现出减少的空间工作记忆，这可能是嗅觉缺陷和短期记忆的结果。AD背景调节HUCAPS诱导的食欲动机和嗅觉辨别力的变化，特别是增强NTg小鼠的嗅觉辨别力。然而，将动机动机的变化建模为空间学习和记忆的协变量，并不支持以下结论：动机差异明显地构成了空间学习和记忆的变化。老年小鼠短期吸入人体相关浓度的周围UFP会导致对多个记忆域（参考和短期记忆）的长期不良反应（测试后1–6.5个月），与AD背景无关。当考虑潜在的协变量，例如动机变化和运动活动时，会出现学习和记忆障碍。这些结果表明，有必要进一步研究UFP暴露对成年后认知作用的潜在机制。