Advanced Environmental Research Institute, Department of Biological Sciences, University of North Texas, Denton, TX, USA.
J Alzheimers Dis. 2020;78(4):1453-1471. doi: 10.3233/JAD-200929.
Multiple studies report a strong correlation between traffic-generated air pollution-exposure and detrimental outcomes in the central nervous system (CNS), including Alzheimer's disease (AD). Incidence of AD is rapidly increasing and, worldwide, many live in regions where pollutants exceed regulatory standards. Thus, it is imperative to identify environmental pollutants that contribute to AD, and the mechanisms involved.
We investigated the effects of mixed gasoline and diesel engine emissions (MVE) on the expression of factors involved in progression of AD in the hippocampus and cerebrum in a young versus aged mouse model.
Young (2 months old) and aged (18 months old) male C57BL/6 mice were exposed to either MVE (300μg/m3 PM) or filtered air (FA) for 6 h/d, 7 d/wk, for 50 d. Immunofluorescence and RT-qPCR were used to quantify oxidative stress (8-OHdG) and expression of amyloid-β protein precursor (AβPP), β secretase (BACE1), amyloid-β (Aβ), aryl hydrocarbon receptor (AhR), cytochrome P450 (CYP) 1B1, angiotensin-converting enzyme (ACE1), and angiotensin II type 1 (AT1) receptor in the cerebrum and hippocampus, in addition to cerebral microvascular tight junction (TJ) protein expression.
We observed age-related increases in oxidative stress, AhR, CYP1B1, Aβ, BACE1, and AT1 receptor in the CA1 region of the hippocampus, and elevation of cerebral AβPP, AhR, and CYP1B1 mRNA, associated with decreased cerebral microvascular TJ protein claudin-5. MVE-exposure resulted in further promotion of oxidative stress, and significant increases in AhR, CYP1B1, BACE1, ACE1, and Aβ, compared to the young and aged FA-exposed mice.
Such findings suggest that MVE-exposure exacerbates the expression of factors in the CNS associated with AD pathogenesis in aged populations.
多项研究报告表明，交通产生的空气污染暴露与中枢神经系统（CNS）的不良后果之间存在很强的相关性，包括阿尔茨海默病（AD）。AD 的发病率正在迅速增加，在全球范围内，许多人生活在污染物超过监管标准的地区。因此，必须确定导致 AD 的环境污染物及其涉及的机制。
我们研究了混合汽油和柴油发动机排放物（MVE）对年轻和老年小鼠模型海马和大脑中 AD 进展相关因素表达的影响。
年轻（2 个月大）和老年（18 个月大）雄性 C57BL/6 小鼠分别暴露于 MVE（300μg/m3 PM）或过滤空气（FA）中 6 小时/天，每周 7 天，持续 50 天。免疫荧光和 RT-qPCR 用于定量氧化应激（8-OHdG）和淀粉样前体蛋白（AβPP）、β 分泌酶（BACE1）、淀粉样蛋白-β（Aβ）、芳烃受体（AhR）、细胞色素 P450（CYP）1B1、血管紧张素转换酶（ACE1）和血管紧张素 II 型 1（AT1）受体在大脑和海马中的表达，以及大脑微血管紧密连接（TJ）蛋白的表达。
我们观察到与年龄相关的海马 CA1 区氧化应激、AhR、CYP1B1、Aβ、BACE1 和 AT1 受体增加，以及大脑 AβPP、AhR 和 CYP1B1 mRNA 升高，与大脑微血管 TJ 蛋白 Claudin-5 减少有关。与年轻和老年 FA 暴露的小鼠相比，MVE 暴露导致氧化应激进一步加剧，AhR、CYP1B1、BACE1、ACE1 和 Aβ 显著增加。
这些发现表明，MVE 暴露加剧了与老年人群 AD 发病机制相关的 CNS 中因素的表达。
