Advanced Environmental Research Institute, Department of Biological Sciences, University of North Texas, Denton, TX, 76201, USA.
Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, 87108, USA.
Toxicol Lett. 2021 Mar 15;339:39-50. doi: 10.1016/j.toxlet.2020.12.016. Epub 2020 Dec 26.
Traffic-generated air pollutants have been correlated with alterations in blood-brain barrier (BBB) integrity, which is associated with pathologies in the central nervous system (CNS). Much of the existing literature investigating the effects of air pollution in the CNS has predominately been reported in males, with little known regarding the effects in females. As such, this study characterized the effects of inhalation exposure to mixed vehicle emissions (MVE), as well as the presence of female sex hormones, in the CNS of female ApoE mice, which included cohorts of both ovariectomized (ov-) and ovary-intact (ov+) mice. Ov + and ov- were placed on a high-fat diet and randomly grouped to be exposed to either filtered-air (FA) or MVE (200 PM/m: 50 μg PM/m gasoline engine + 150 μg PM/m from diesel engine emissions) for 6 h/d, 7d/wk, for 30d. MVE-exposure resulted in altered cerebral microvascular integrity and permeability, as determined by the decreased immunofluorescent expression of tight junction (TJ) proteins, occludin, and claudin-5, and increased IgG extravasation into the cerebral parenchyma, compared to FA controls, regardless of ovary status. Associated with the altered cerebral microvascular integrity, we also observed an increase in matrix metalloproteinases (MMPs) -2/9 activity in the MVE ov+, MVE ov-, and FA ov- groups, compared to FA ov+. There was also elevated expression of intracellular adhesion molecule (ICAM)-1, inflammatory interleukins (IL-1, IL-1β), and tumor necrosis factor (TNF-α) mRNA in the cerebrum of MVE ov + and MVE ov- animals. IκB kinase (IKK) subunits IKKα and IKKβ mRNA expressions were upregulated in the cerebrum of MVE ov- and FA ov- mice. Our findings indicate that MVE exposure mediates altered integrity of the cerebral microvasculature correlated with increased MMP-2/9 activity and inflammatory signaling, regardless of female hormones present.
交通产生的空气污染物与血脑屏障 (BBB) 完整性的改变有关，而 BBB 完整性的改变与中枢神经系统 (CNS) 的病理学有关。现有的大量研究空气污染对中枢神经系统影响的文献主要是在雄性动物中报道的，而关于雌性动物的影响则知之甚少。因此，本研究描述了吸入混合车辆排放物 (MVE) 以及雌性激素存在的情况下，对雌性 ApoE 小鼠中枢神经系统的影响，其中包括卵巢切除 (ov-) 和卵巢完整 (ov+) 两组小鼠。ov+ 和 ov- 被喂食高脂肪饮食，并随机分为暴露于过滤空气 (FA) 或 MVE (200 PM/m: 50 μg PM/m 汽油发动机+150 μg PM/m 柴油发动机排放物) 组，每天 6 小时，每周 7 天，共 30 天。与 FA 对照组相比，MVE 暴露导致大脑微血管完整性和通透性改变，表现为紧密连接 (TJ) 蛋白、occludin 和 claudin-5 的免疫荧光表达减少，以及 IgG 渗漏到大脑实质中，而与卵巢状态无关。与大脑微血管完整性改变相关的是，我们还观察到 MVE ov+、MVE ov- 和 FA ov- 组中基质金属蛋白酶 (MMPs) -2/9 的活性增加，而 FA ov+ 组没有。MVE ov+ 和 MVE ov- 动物大脑中的细胞间黏附分子 (ICAM)-1、炎症性白细胞介素 (IL-1、IL-1β) 和肿瘤坏死因子 (TNF-α) mRNA 的表达也升高。MVE ov- 和 FA ov- 小鼠大脑中的 IκB 激酶 (IKK) 亚单位 IKKα 和 IKKβ mRNA 的表达上调。我们的研究结果表明，MVE 暴露会导致大脑微血管完整性改变，与 MMP-2/9 活性和炎症信号增加有关，而与雌性激素的存在无关。
