Exposure to ambient air pollution has been associated with both cognitive impairment and cardiac dysfunction and a post-mortem study reported evidence of accumulation of amyloid among people living in cities with high levels of ambient pollution. Whether exposure to high levels of air pollution accelerates the formation of aggregates is unknown. We propose a 3 month controlled exposure experiment in Alzheimer?s prone mice carrying the single mutation in the in the Presenilin-1 gene (PSEN1) (PS1?E9) or the double mutation in the APPswe + the PS1?E9 (APPswe/PS1?E9). All mice are in the C57/Bl6J background and C57/Bl6J wild-type mice will serve as controls. Mice will be exposed beginning at age 3 months to evaluate the impact of concentrated fine particulate matter (PM2.5) versus filtered air (FA) exposure on brain and cardiac structure and function. Mice will be studied at two time points: immediately after the exposure and at the end of the 3-month exposure. Another set of mice will be exposed to PM2.5 for 3 month than for FA for 3 more months. A control group will be exposed to FA for 6 month. We hypothesize that Alzheimer?s prone mice exposed to PM2.5 will develop: 1) a greater quantity of aggregates in the specific anatomical regions of the brain and heart as assessed by imaging and electron microscopy; 2) worsen brain function assessed with behavioral studies and cardiac function assessed by echocardiography, biometric measurements in-vivo and worsen calcium homeostasis in primary neurons and contractile function and calcium handling in isolated cardiomyocytes in-vitro. We also hypothesize that exposure to PM will accelerate amyloid pathology by inducing oxidative stress.

Public Health Relevance

Exposure to ambient pollution is responsible for more than 13 million deaths annually (World Health Organization) and it has been associated with cardiovascular morbidity and mortality, and with poorer cognitive function in the aging population. Whether individually, Alzheimer dementia and heart failure are a growing plague worldwide, the recognition of their combinatory triggers and potential coexistence is an alarming prospective. In this proposal, we will explore the role and mechanisms by which air pollution induce the development and progression of brain and heart diseases since both are worsened by exposures.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Opanashuk, Lisa A
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Ohio State University
Schools of Nursing
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Tanwar, Vineeta; Katapadi, Aashish; Adelstein, Jeremy M et al. (2018) Cardiac pathophysiology in response to environmental stress: a current review. Curr Opin Physiol 1:198-205
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