# Combined environmental exposures and neurodevelopment disorders

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $241,250

## Abstract

Project Summary/Abstract: Autism spectrum disorders (ASD) are pervasive, highly prevalent lifelong
disorders for which pharmacological interventions are not readily available. While genetic factors are likely
contributors to these disorders, heritability estimates indicate strong environmental contributions. Of significant
interest is the link between fetal gestation and the activation of the maternal immune system during critical
periods of development. Epidemiological reports suggest a strong association between periods of maternal
immune activation - including immune conditions such as allergies and asthma - and an increased risk of
having a child with ASD. Acute exacerbations are common in pregnant asthmatic women, with as many as
35% suffering attacks requiring hospitalization. In addition, particulate matter from air pollution, a major
exacerbating factor in allergic asthma, has been linked with an increased risk for ASD. This is particularly
concerning given the increasing presence of particulate matter from wildfires, which are becoming more
frequent and severe. Despite this, the consequences of gestational exposure to maternal asthma/allergy-
mediated responses, wildfire particulate matter (WPM), or their combined effects on fetal development remain
largely unknown. We recently developed a preclinical model of maternal allergic asthma (MAA) during
gestation that alters neurobiology and microglial function and disrupts epigenetic mechanisms in offspring. We
have WPM samples collected in situ and through proximity sampling of wildfire emissions, capturing the
complexity of real-world complex WPM exposures. We will test the innovative hypothesis that WPM and MAA
combined are causally linked to altered microglia activation and function and that these exposures lead to
epigenetic modifications of microglia that will enable us to discover gene pathways that diverge or converge
between the two exposures. The proposed studies will examine WPM alone and the exacerbating effects of
WPM sampled from the Northern California region during fire season plus MAA on microglia activation and
function (Aim #1). Environmental exposures during critical windows in early life can impact epigenetic
mechanisms, and the developing brain is particularly susceptible to these changes. Over-activation of the
maternal immune system, for instance, can lead to an over-activation of the fetal immune system, potentially
hindering brain development. We will test the hypothesis that epigenetic mechanisms in microglia are altered
by combined WPM + MAA (Aim #2). If successful, this research will validate the concept that
neurodevelopmental disorders such as ASD is, for some, caused by environmental contaminants that alter
immune mechanisms. Our findings could identify novel mechanisms and preventative strategies for one of the
most visible public health concerns of our time.

## Key facts

- **NIH application ID:** 10889670
- **Project number:** 1R21ES035969-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Paul Ashwood
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $241,250
- **Award type:** 1
- **Project period:** 2024-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10889670

## Citation

> US National Institutes of Health, RePORTER application 10889670, Combined environmental exposures and neurodevelopment disorders (1R21ES035969-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10889670. Licensed CC0.

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