# Gene-environment interactions in the developmental neurotoxicity of air pollution

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $336,872

## Abstract

Increasing  evidence  from  human  epidemiological  and  animal  studies  suggests  that  air  pollution  may
negatively affect the central nervous system (CNS) and contribute to CNS  diseases.  Traffic-related  air pollution is a major contributor to global air pollution, and diesel exhaust (DE) is its most important component. Several studies suggest that young individuals may be particularly susceptible to air pollution-induced neurotoxicity, and that perinatal exposure may cause or contribute to developmental disabilities and behavioral abnormalities. In particular, a number of recent studies have found associations between exposures to traffic-related air pollution and autism spectrum disorders (ASD), which is characterized by impairment in socialization and in communication, and by the presence of repetitive and unusual behaviors. The cause(s) of ASD are unknown, and while it may have a hereditary component, environmental factors are increasingly suspected as playing a pivotal role in its etiology, particularly in genetically susceptible individuals. Autistic children present higher levels of neuroinflammation and systemic inflammation, which are also hallmarks of exposure to traffic-related air pollution. In a series of preliminary studies we have found that perinatal exposure of mice to DE (from gestational day 0 to postnatal day 21) caused a number of behavioral alterations in the domains relevant to ASD (communication, sociability, repetitive behaviors). The aim of the  present proposal is to  investigate biochemical, molecular, and  morphological alterations caused by developmental DE exposure that may be relevant for ASD. In particular, we will  test  the hypothesis that DE-induced neuroinflammation will alter a signaling cascade leading, through epigenetic changes, to a decreased expression of reelin, and this in turn will affect cortical morphogenesis and cause disruption of cortical layering, as seen in ASD. We will also investigate gene-environment interactions by assessing the developmental neurotoxicity of DE exposure in reelin heterozygous mice (rl+/%) and in Gclm+/% mice. The rl+/% mice will allow a direct testing of the “reelin hypothesis”  and are  expected to be more susceptible to the effects of DE. The Gclm+/%  mice are a model for a very common genetic polymorphism, and we have shown that they are more susceptible to acute DE neurotoxicity. Altogether, these studies will provide evidence on the ability of DE, as an indicator of traffic-related air pollution, to cause behavioral, biochemical and  morphological alterations which may be relevant to  ASD, and  will provide  evidence  of novel gene-environment interactions.

## Key facts

- **NIH application ID:** 10224197
- **Project number:** 5R01ES028273-05
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** LUCIO G COSTA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $336,872
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10224197

## Citation

> US National Institutes of Health, RePORTER application 10224197, Gene-environment interactions in the developmental neurotoxicity of air pollution (5R01ES028273-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10224197. Licensed CC0.

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