# Long-Term Neurodegenerative Consequences of Air Pollution Exposure during Pregnancy

> **NIH NIH R01** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2021 · $278,468

## Abstract

SUMMARY: Air pollution exposure has well-appreciated negative impacts on cardiovascular, pulmonary and
neurological systems, including numerous epidemiological and toxicological reports documenting increased
risk for Alzheimer’s Disease (AD). During pregnancy, unique molecular adaptations of the cerebral
endothelium occur to counteract the effects of circulating vasoactive factors and preserve BBB properties and
brain homeostasis. While these adaptations appear to maintain brain homeostasis during gestation,
vulnerability to neuroinflammatory responses to inhaled toxicant-induced circulatory factors are unstudied.
Importantly, hypertensive disorders of pregnancy represent a major risk factor for the development of AD in
later life – and air pollution exposure can promote gestational hypertensive scenarios. Inhaled ozone (O3)
induces proteolytic activity in the lung, leading to shredding of protein fragments into the circulation that are
bioreactive, promoting cerebrovascular endothelial inflammatory reactions. Our prior reports demonstrated that
acute air pollutant exposure thusly impairs blood-brain barrier and activates central nervous system (CNS) glia
(microglia and astrocytes) in brain regions, including the cortex, limbic structures and in the cerebellum,
regions essential for learning, memory and cognition. Neurodegenerative sequelae such as pathological β-
amyloid accumulation was observed following an acute exposure of O3 in rodents with advanced age.
Neuroinflammation plays a pivotal role in the pathobiology of AD. β-amyloid accumulation and pathological tau
protein phosphorylation leading to formation of neurofibrillary tangles (referred as taupathy) are hallmarks of
AD pathology leading to dementia, deficits in cognitive and memory function, all of which are potentiated by
neuroinflammation. Neuroinflammatory events from air pollutant exposure, compounded by hypertensive
conditions during gestation, may dispose women to greater risk of AD-associated pathology in later-life. In the
parent R01, we have identified O3-induced cardiovascular and placental dysfunctional sequelae similar to
preeclampsia. We wish to now examine the long-term consequences of pollution-induced neuroinflammation in
the maternal brain in the context of taupathy and AD. We hypothesize that the combined neuroinflammatory
and gestational hypertensive consequences of gestational air pollution exposure augment risk taupathy in
later-life. To test this, we will first assess the extent to which gestational exposure to O3 exacerbates acute
neuroinflammatory effects compared non-pregnant mouse exposures. Secondly, we will determine whether O3
exposure-induced neuroinflammation during pregnancy accelerates the onset of taupathy and exacerbates the
magnitude of taupathy and neuroinflammation. Using wildtype and Tau P301S transgenic mice (mutant human
microtubule-associated protein tau), we will examine the long-term effects of O3 exposure on the onset of
taupathy and magnit...

## Key facts

- **NIH application ID:** 10287863
- **Project number:** 3R01ES014639-14S1
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Matthew J Campen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $278,468
- **Award type:** 3
- **Project period:** 2008-05-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10287863

## Citation

> US National Institutes of Health, RePORTER application 10287863, Long-Term Neurodegenerative Consequences of Air Pollution Exposure during Pregnancy (3R01ES014639-14S1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10287863. Licensed CC0.

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