Exposure to Traffic-Generated Pollutants Exacerbates the Expression of Factors Associated with the Pathophysiology of Alzheimer’s Disease in Aged C57BL/6 Wild-Type Mice

Abstract

Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: Such findings suggest that MVE-exposure exacerbates the expression of factors in the CNS associated with AD pathogenesis in aged populations.

Peripheral HMGB1 is linked to O3 pathology of disease‐associated astrocytes and amyloid

“…Alzheimer's disease (AD) is the most common neurodegenerative disease and the leading cause of dementia; however, its etiology is largely unknown, and there are few disease‐modifying treatments. 1 , 2 Increasing evidence points to a role for environmental factors in AD risk, 3 , 4 , 5 , 6 , 7 , 8 with several studies implicating several components of urban air pollution in increased AD risk and cognitive deficits. 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 Urban air pollution is a complex mixture comprising several chemical, particulate, and gaseous components, such as ozone (O 3 ), which is a prevalent and chronic exposure with health effects spanning several organ systems, 18 , 19 including the central nervous system (CNS).…”