Exposure to traffic-generated air pollution promotes alterations in the integrity of the brain microvasculature and inflammation in female ApoE-/- mice. (15th March 2021)

• Record Type: Journal Article
• Authors: Adivi, Anna; Lucero, JoAnn; Simpson, Nicholas; McDonald, Jacob D.; Lund, Amie K.
• Is Part Of: Toxicology letters. Volume 339(2021)
• Page Start: 39
• Page End: 50
• Publication Date: 2021-03-15
• Subjects: Apo E−/− Apolipoprotein E null mouse -- BBB blood brain barrier -- CNS central nervous system -- FA filtered air -- ICAM intracellular adhesion molecule -- IgG immunoglobin G -- IKK IκB kinase (IKK) -- IKKα IKK alpha -- IKKβ IKK beta -- ILs interleukins -- IL-1β Interleukin-1 beta -- MMPs metalloproteinase -- MS Multiple Sclerosis -- MVE mixed vehicle exhaust -- NOx nitrogen oxides -- NO2 nitrogen dioxide -- NF-κB nuclear factor kappa B -- Ov+ ovary intact female mice -- Ov- ovariectomized female mice -- PM particulate matter -- RelA v-rel avian reticuloendotheliosis viral oncogene homolog A (p65) -- ROS reactive oxygen species -- TJ tight junction -- TNF-α tumor necrosis factor alpha -- VCAM vascular cell adhesion molecule; Air pollution -- Female -- Brain -- Inflammatory markers -- BBB integrity; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2020.12.016
• Languages: English
• ISSNs: 0378-4274

Abstract

Graphical abstract: Highlights: Vehicle emissions alters cerebral microvascular integrity in female ApoE-/- Mice. Inhaled vehicle exhaust increases cerebral microvascular MMP-2/9 activity. Ovarian presence protects against MVE-effects on the brain microvascular integrity. Vehicle exhaust-exposure induces neuroinflammation, regardless of presence of ovaries. NF-κB regulatory factors are upregulated in ovariectomized and MVE-exposed females. Abstract: 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 3 : 50 μg PM/m 3 gasoline engine + 150 μg PM/m 3 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.