# Woods Hole Center for Oceans and Human Health

> **NIH NIH P01** · WOODS HOLE OCEANOGRAPHIC INSTITUTION · 2021 · $30,662

## Abstract

Project Summary
The research proposed in this supplement tests the hypothesis that developmental domoic acid (DA)
exposure affects microglia, the resident immune cells in the brain, resulting in altered function,
impacts on neuron health, and neurobehavioral deficits. Microglia play an important role in
inflammation and responding to immune challenge in the brain. Microglial dysfunction in development
can be caused by exposure to environmental chemicals and can lead to changes in brain structure,
function, and neurobehavior. Early life impacts on microglia can have far-reaching impacts, including
increased sensitivity to subsequent stressors causing elevated neuroinflammation and eventual
neurodegeneration. Despite the importance of this cell type, very little is known about the role of
microglia in mediating the effects of harmful algal toxins, including DA. The proposed research will
investigate the impacts of developmental DA on microglial activation and assess the impacts of early
life inflammation on neuronal survival and learning. In specific aim 1, we test the hypothesis that
developmental DA exposure causes microglial activation in zebrafish brain. We will utilize confocal
imaging and transgenic zebrafish expressing cell-specific fluorescent markers to assess changes in
microglial morphology indicative of activation. This study will also identify windows of susceptibility. In
specific aim 2, we will investigate the impacts of developmental exposure on sensitivity to later life
insults. We will test the hypothesis that developmental exposure to DA will cause increased
inflammation and neurodegeneration, as well as neurobehavioral changes, in response to exposure in
adult fish. This aim will utilize well-characterized behavioral assays of associative learning and
histological markers of neuroinflammation and neurodegeneration. In specific aim 3, we will test the
hypothesis that developmental DA exposure causes altered gene expression and upregulation of
inflammatory factors in microglia. We will characterize the microglia-specific transcriptional profiles
associated with DA exposure using fluorescence-activated cell sorting followed by RNA sequencing.
The results from the proposed study will provide important information about the role of microglia as a
potential target of domoic acid, and the risks of developmental exposure.

## Key facts

- **NIH application ID:** 10225184
- **Project number:** 3P01ES028938-03S1
- **Recipient organization:** WOODS HOLE OCEANOGRAPHIC INSTITUTION
- **Principal Investigator:** JOHN J STEGEMAN
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $30,662
- **Award type:** 3
- **Project period:** 2018-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225184

## Citation

> US National Institutes of Health, RePORTER application 10225184, Woods Hole Center for Oceans and Human Health (3P01ES028938-03S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10225184. Licensed CC0.

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