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The Effects of Chronic Exposure to Ambient Traffic-Related Air Pollution on Alzheimer’s Disease Phenotypes in Wildtype and Genetically Predisposed Male and Female Rats
Environmental Health Perspectives ( IF 10.4 ) Pub Date : 2021-5-10 , DOI: 10.1289/ehp8905
Kelley T Patten 1 , Anthony E Valenzuela 1 , Christopher Wallis 2 , Elizabeth L Berg 3 , Jill L Silverman 3, 4 , Keith J Bein 2, 5 , Anthony S Wexler 2, 6 , Pamela J Lein 1, 4
Affiliation  

Abstract

Background:

Epidemiological data link traffic-related air pollution (TRAP) to increased risk of Alzheimer’s disease (AD). Preclinical data corroborating this association are largely from studies of male animals exposed acutely or subchronically to high levels of isolated fractions of TRAP. What remains unclear is whether chronic exposure to ambient TRAP modifies AD risk and the influence of sex on this interaction.

Objectives:

This study sought to assess effects of chronic exposure to ambient TRAP on the time to onset and severity of AD phenotypes in a preclinical model and to determine whether sex or genetic susceptibility influences outcomes.

Methods:

Male and female TgF344-AD rats that express human AD risk genes and wildtype littermates were housed in a vivarium adjacent to a heavily trafficked tunnel in Northern California and exposed for up to 14 months to filtered air (FA) or TRAP drawn from the tunnel and delivered to animals unchanged in real time. Refractive particles in the brain and AD phenotypes were quantified in 3-, 6-, 10-, and 15-month-old animals using hyperspectral imaging, behavioral testing, and neuropathologic measures.

Results:

Particulate matter (PM) concentrations in TRAP exposure chambers fluctuated with traffic flow but remained below 24-h PM with aerodynamic diameter less than or equal to 2.5 micrometers (PM2.5) U.S. National Ambient Air Quality Standards limits. Ultrafine PM was a predominant component of TRAP. Nano-sized refractive particles were detected in the hippocampus of TRAP animals. TRAP-exposed animals had more amyloid plaque deposition, higher hyperphosphorylated tau levels, more neuronal cell loss, and greater cognitive deficits in an age-, genotype-, and sex-dependent manner. TRAP-exposed animals also had more microglial cell activation, but not astrogliosis.

Discussion:

These data demonstrate that chronic exposure to ambient TRAP promoted AD phenotypes in wildtype and genetically susceptible rats. TRAP effects varied according to age, sex, and genotype, suggesting that AD progression depends on complex interactions between environment and genetics. These findings suggest current PM2.5 regulations are insufficient to protect the aging brain. https://doi.org/10.1289/EHP8905



中文翻译:

慢性暴露于环境交通相关空气污染对野生型和遗传易感雄性和雌性大鼠阿尔茨海默病表型的影响

摘要

背景:

流行病学数据将交通相关的空气污染 (TRAP) 与阿尔茨海默病 (AD) 的风险增加联系起来。证实这种关联的临床前数据主要来自对雄性动物急性或亚慢性暴露于高水平分离的 TRAP 部分的研究。目前尚不清楚的是,长期暴露于环境 TRAP 是否会改变 AD 风险以及性别对这种相互作用的影响。

目标:

本研究试图在临床前模型中评估长期暴露于环境 TRAP 对 AD 表型发病时间和严重程度的影响,并确定性别或遗传易感性是否会影响结果。

方法:

表达人类 AD 风险基因的雄性和雌性 TgF344-AD 大鼠和野生型同窝仔鼠被安置在靠近北加州一条交通繁忙的隧道的饲养箱中,并暴露于从隧道抽取的过滤空气 (FA) 或 TRAP 中长达 14 个月,实时交付给动物。使用高光谱成像、行为测试和神经病理学测量对 3、6、10 和 15 个月大的动物大脑中的屈光颗粒和 AD 表型进行量化。

结果:

TRAP 暴露室中的颗粒物 (PM) 浓度随交通流量而波动,但仍低于 24 小时 PM,空气动力学直径小于或等于 2.5 微米 (下午2.5) 美国国家环境空气质量标准限制。Ultrafine PM 是 TRAP 的主要成分。在 TRAP 动物的海马体中检测到纳米级折射颗粒。暴露于 TRAP 的动物具有更多的淀粉样蛋白斑块沉积、更高的过度磷酸化 tau 水平、更多的神经元细胞损失,以及年龄、基因型和性别依赖性方式的更大认知缺陷。暴露于 TRAP 的动物也有更多的小胶质细胞活化,但没有星形胶质细胞增生。

讨论:

这些数据表明,长期暴露于环境 TRAP 会促进野生型和遗传易感大鼠的 AD 表型。TRAP 效应因年龄、性别和基因型而异,这表明 AD 进展取决于环境和遗传之间的复杂相互作用。这些发现表明当前下午2.5法规不足以保护老化的大脑。https://doi.org/10.1289/EHP8905

更新日期:2021-05-11
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