# Investigating the role of neuroinflammation in environmental exposure-induced anxiety disorders

> **NIH NIH R21** · WOODS HOLE OCEANOGRAPHIC INSTITUTION · 2024 · $206,250

## Abstract

Project Summary
This R21 proposal tests the hypothesis that environmental chemicals target microglia, the resident
immune cells in the brain and alterations in microglial function contributes to the risk of development
of neuropsychiatric and neurodegenerative disorders. Microglia play an important role in responding
to inflammation and immune challenge in the brain. They also have been shown to have a number of
important roles beyond immune response, including synaptic pruning during development and adult
neurogenesis. Microglial activation has been shown to be involved in the progression of different
neurodegenerative diseases as well as in several neuropsychiatric conditions. Accumulating evidence
suggests that environmental chemical exposure increases the susceptibility to the development of
various neurodegenerative and neuropsychiatric disorders. A majority of the studies investigating the
impacts of environmental chemical exposure on microglia have been conducted using in vitro cell
culture systems and very little is known about in vivo effects, especially during early life.
The proposed research is aimed at understanding the role of environmental chemical exposure on
microglial dysfunction in vivo in a well-established developmental model system using imaging,
molecular and behavioral approaches. It has two specific aims. In specific aim 1, we test the
hypothesis that exposure of zebrafish to polychlorinated biphenyls (PCBs) causes microglial
activation. These studies will be conducted using a range of environmentally relevant concentrations
of PCB126, a dioxin-like PCB that is ubiquitously distributed in the environment. Using transgenic
zebrafish expressing cell-specific fluorescent markers and time-lapse confocal imaging, we will
measure microglial morphology in response to exposure. In addition, the potential effects of microglial
activation on neuronal network as well as neurobehaviors will be quantified. In specific aim 2, we will
test the hypothesis that PCB-induced microglia dysfunction is AHR dependent. Using AHR null
zebrafish, we will characterize the role of AHR in microglial activation. Wild type and AHR null
zebrafish will be exposed to a concentration of PCB126 that affected microglia and characterize the
effects both immediately after exposure and later in life. We will characterize the brain specific
transcriptional and epigenetic profiles associated with these changes using single cell RNA
sequencing and single cell DNA methylation profiling. The results from the proposed studies will
provide fundamental knowledge about the role of environmental chemicals on immune cells in the
brain.

## Key facts

- **NIH application ID:** 10750984
- **Project number:** 5R21ES034839-02
- **Recipient organization:** WOODS HOLE OCEANOGRAPHIC INSTITUTION
- **Principal Investigator:** NEELAKANTESWAR Aluru
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $206,250
- **Award type:** 5
- **Project period:** 2022-12-09 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10750984

## Citation

> US National Institutes of Health, RePORTER application 10750984, Investigating the role of neuroinflammation in environmental exposure-induced anxiety disorders (5R21ES034839-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10750984. Licensed CC0.

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