# Lead (Pb) toxicity on mechanisms of neurodevelopment by dysregulation of thyroid hormone distributor proteins in Xenopus laevis

> **NIH NIH F31** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2021 · $38,826

## Abstract

Project Summary
Environmental exposure to lead (Pb) during pre- and perinatal development is associated with an increase in
neurodevelopmental deficits and neurological abnormalities. While it has long been established that Pb is
neurotoxic, the precise mechanisms of toxicity are not entirely clear. Previous studies showed that Pb impairs
thyroid hormone (TH) physiology. The precise mechanisms of Pb-induced dysregulation of thyroid hormone
signaling have not been elucidated, however, and the downstream effects of TH dysregulation on brain
development have not been assessed. Therefore, the goal of the proposed research is to investigate the
effects of Pb on thyroid hormone physiology and on TH-mediated mechanisms of brain development. To
address this goal, the Thompson lab has used Xenopus laevis tadpoles, an NIH-validated model organism
allowing developmental access to toxicological endpoints, to study the effects of developmental exposure to
endocrine disrupting compounds on the developing brain. Based on previously published studies suggesting
Pb’s ability to impact TH physiology, Preliminary experiments shows that Pb poisoning decreases expression
of two thyroid hormone distributor proteins (THDPs), transthyretin and lipocalin-like prostaglandin D2 synthase,
in the liver and the brain, respectively. Downregulation of THDPs likely decreases the amount of TH that
reaches brain tissues. The specific effects of these changes on brain development have not been assessed.
The aims of this project propose to fill in this important gap by determining the physiological processes by
which Pb exerts these effects on TH-dependent cellular and molecular mechanisms of development, with
emphasis on neurodevelopment. The Amphibian Metamorphosis Assay will be used to test if Pb poisoning
affects overall TH physiology. The effects of decreased THDP expression in the brain will be assessed by
quantifying neurogenesis, dendritic arborization, and expression of TH-sensitive genes. The proposed work will
provide information regarding the aspects of the HPT axis that are dysregulated by Pb during development as
well as how this affects various aspects of brain development. These studies will provide insight into the
mechanisms of Pb-induced neurotoxicity and potentially yield a target for future clinical studies aiming to
decrease the negative effects of Pb poisoning in children.

## Key facts

- **NIH application ID:** 10249964
- **Project number:** 5F31ES031855-02
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Lara Iza DaHora
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,826
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249964

## Citation

> US National Institutes of Health, RePORTER application 10249964, Lead (Pb) toxicity on mechanisms of neurodevelopment by dysregulation of thyroid hormone distributor proteins in Xenopus laevis (5F31ES031855-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10249964. Licensed CC0.

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