# Assessing risks for Alzheimer's disease induced by exposure to environmental pesticides

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2022 · $400,000

## Abstract

ABSTRACT
The role of pesticide exposure in Alzheimer’s disease (AD) has long been suspected, but the specific causative
agents and the mechanisms underlying are not fully understood
. The goal of this proposal is to evaluate the
risk for AD pathology in an animal model of early-life exposure to the pyrethroid deltamethrin (DM), a
commonly use pesticide, and to assess potential therapeutic strategies to treat related memory loss in this
model.
Evidence indicates that DM exerts strong stimulatory effects on voltage-gated Na+ (Nav) Nav1.6 channels that
are abundantly expressed in CA1 hippocampal pyramidal neurons and play a critical role in action potential
initiation and propagation. During AD progression, the hippocampus is the principal brain region to display
altered activity. In early phases of the disease, hyperexcitability of the hippocampal circuit caused by
dysregulation of ion channels modulating the intrinsic properties of hippocampal neurons, has been ascribed
as the triggering event preceding the global decline of synaptic function that characterizes late phases of the
disease. Specifically, hyperactivity of Nav1.6 in the hippocampus and consequently increased firing frequency
of CA1 pyramidal neurons is one of the first signs of hippocampal neurodegeneration in early-phase AD. Using
a combination of MALDI imaging, immunohistochemistry, electrophysiological and behavioral assays, we will
assess the influence of early-life DM exposure on Ab synaptic pathology (Aim 1), hippocampal dysfunction
(Aim 2) and memory loss (Aim 3) and evaluate in vivo gene silencing targeting Nav1.6 as a therapeutic
strategy for AD pathology exacerbated by pyrethroid exposure. Outcomes of this study will provide new
knowledge on the gene-environment interactions underlying risk of AD.

## Key facts

- **NIH application ID:** 10499574
- **Project number:** 3R01ES031823-03S1
- **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:** $400,000
- **Award type:** 3
- **Project period:** 2020-09-28 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499574

## Citation

> US National Institutes of Health, RePORTER application 10499574, Assessing risks for Alzheimer's disease induced by exposure to environmental pesticides (3R01ES031823-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10499574. Licensed CC0.

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