# Environmental Toxins and Microglia-Synapse Interactions in Autism

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $463,496

## Abstract

Project Summary
Environmental toxins and microglia-synapse interactions in autism.
It is increasingly evident that diverse genes and environmental exposure(s) combine or synergize to produce a
spectrum of autism phenotypes dependent upon critical developmental windows. Multiple prenatal/maternal
environmental toxins and exposures have been linked to human ASDs, but the associations of single agents
have been relatively weak. This suggests it is the combination of multiple maternal exposures that increases
vulnerability in offspring. We now recognize that non-chemical stressors, such as limited resources or social
support of the mother, can increase vulnerability of the fetus to chemical stressor exposures (e.g., pollution or
toxins), which could explain why a single exposure or risk factor in isolation is a modest predictor of autism
risk. Models aimed at deciphering the mechanisms that contribute to ASD suffer from oversimplification, using
single agents. We breach this gap by using a new model that employs the combined effects of an ethologically
relevant maternal stressor and environmentally relevant pollutant, diesel exhaust, both of which have been
implicated in autism. We show that maternal diesel exhaust particle (DEP) exposure combined with maternal
stress (MS) (but neither in isolation) produces early-life communication deficits, and long-term cognitive deficits
and strikingly increased anxiety in male but not female offspring. We show evidence that DEP exposure
significantly alters microglial colonization of the male but not female embryonic brain, and combined prenatal
DEP and MS exposure leads to persistent changes in the function of microglia of the same brain regions of
males. Beyond their functions in innate immune defense of the brain, microglia are important regulators of
experience-dependent synaptic remodeling during development. It is proposed that microglia prune
inappropriate or weak synapses while sparing appropriate or strong connections. Autism has been well
described as a disease of synaptic dysfunction, and functional network analyses have nearly all pointed out the
importance of molecular pathways that control activity-dependent synaptic remodeling in the pathology of
ASDs. Importantly, impaired microglia-mediated pruning in mice disrupts functional brain connectivity and
social behavior, strongly suggesting that microglia-synapse interactions may contribute to autism’s
pathophysiology. Thus, the specific hypothesis to be tested here is that microglial activation by combined
environmental factors will cause aberrant synaptic pruning by these cells, leading to neural circuit
dysfunction and ASD-like behaviors.

## Key facts

- **NIH application ID:** 10019548
- **Project number:** 5R01ES025549-05
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Staci D Bilbo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $463,496
- **Award type:** 5
- **Project period:** 2016-09-30 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019548

## Citation

> US National Institutes of Health, RePORTER application 10019548, Environmental Toxins and Microglia-Synapse Interactions in Autism (5R01ES025549-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10019548. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*