# Neurotoxicology of deltamethrin in the developing brain

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2022 · $486,863

## Abstract

ABSTRACT
Epidemiological studies identify early life exposure to pyrethroids as a threatening risk factor for attention-
deficit hyperactivity disorder (ADHD). Because the reported risk of exposure is within no-observed-adverse-
effect level (NOAEL) guidelines, environmental exposure to pyrethroids could be an underestimated leading
cause of ADHD and other neurodevelopmental disorders in the general population. Animal models of early-life
exposure to the pyrethroid pesticide deltamethrin (DM), a potent neurotoxin that acts on the insect voltage-
gated Na+ (Nav) channel, recapitulates ADHD-like behavior through disruption of dopamine signaling in the
nucleus accumbens (NAc), the brain region implicated in the human disease. Yet, the mechanism of toxicity of
DM in the developing brain has not yet been determined. Recent studies from our group provide evidence for
cross reactivity of DM with the mammalian Nav1.1 channel, an isoform expressed in fast-spiking parvalbumin
(PV) inhibitory interneurons during development. These cells exert a powerful inhibitory control over the output
of the NAc, which, if disrupted, leads to dopamine dysfunction with effects on locomotor activity, attention, and
impulsivity, endophenotypes that characterize ADHD. In supporting studies conducted in an early-life DM
exposure animal model we show regional accumulation of DM and loss in GABA in the NAc/striatum and
demonstrate disruption of PV interneuron firing in the same brain region accompanied by ADHD-like behaviors.
Building on this premise, we propose molecular (Aim 1), functional (Aim 2) and behavioral (Aim 3) studies to
test the hypothesis that the primary mechanism of DM toxicity in the developing brain is to disrupt PV
interneuron function leading to loss of local inhibitory control in the NAc and behavioral phenotypes common to
ADHD. Outcomes of this study will provide new insights into the molecular-based understanding of risk factors
for neurodevelopmental disorders providing guidance for therapeutic development against exposure.

## Key facts

- **NIH application ID:** 10430263
- **Project number:** 5R01ES031823-03
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Thomas Arthur Green
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $486,863
- **Award type:** 5
- **Project period:** 2020-09-28 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10430263

## Citation

> US National Institutes of Health, RePORTER application 10430263, Neurotoxicology of deltamethrin in the developing brain (5R01ES031823-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10430263. Licensed CC0.

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