Does lead (PB) poisoning impair brain development by affecting how thyroid hormone gets into the brain?

Active Project Grant Awarded Last action

Award ID
R01ES035813
Recipient
Awarding agency
Obligated
$960,000

Award facts

Assistance listing
93.113 Environmental Health
Completion date 44% complete
Originally
Place of performance
Blacksburg, VA 24061, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Lead (PB) poisoning is a persistent health issue in the united states due to legacy contamination from PB-based sources such as paint, plumbing, and gasoline. Children are most susceptible to PB poisoning, which causes persistent cognitive deficits and low IQ. The specific mechanisms by which PB poisoning impacts development are not fully understood, however. Previous research showed that PB impacts several thyroid hormone (TH)-related processes, including decreases in expression of TH distributor proteins (THDPS) in the choroid plexus. This is an important issue because TH is a critical regulator of brain development; disrupted TH signaling in utero leads to smaller brain size and mental retardation. The impact of PB-induced thdp impairment on development has not been fully tested. Given the impact of PB on thdp expression, our central hypothesis is that PB poisoning impairs TH distribution into the brain and compromises TH-dependent developmental mechanisms. TH regulates important aspects of brain development in both humans and amphibian, in some surprisingly similar ways. The overall rationale of this proposal is that TH is the key driver of metamorphosis in frogs, which makes tadpoles ideally suited to address how PB dysregulates TH-dependent mechanisms of development. We will use xenopus laevis tadpoles to assess the impact of PB on the expression and function of THDPS in the choroid plexus and its effects on TH-sensitive cellular and molecular mechanisms brain development. The central hypothesis will be tested in three specific aims: 1) to determine the effects of PB poisoning on expression of THDPS, TH-sensitive genes, neurogenesis, neuronal differentiation, and spine maturation using time-lapse in vivo imaging techniques. 2) to test if knockdown of thdp expression in the choroid plexus mimics the effects of PB poisoning. 3) to test if overexpression of THDPS in the choroid plexus can counter the effects of PB-poisoning on TH- dependent mechanisms of brain development. The outcomes of this research will test a significantly understudied mechanism by which PB is hypothesized to compromise development. These protocols will serve as a new, unique set of sensitive end points to evaluate not just heavy metals but any chemical suspected of disrupting thdp expression and function. This proposal is innovative because IT uses advanced techniques that have not been previously used in animals to address the issue of developmental PB neurotoxicity. This project is significant because IT will conclusively test the degree to which PB affects development via dysregulation of TH-signaling and therefore may lead to alternative/complimentary therapies for counteracting PB-poisoning in children.

Transactions

Action Obligated Date
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Amendment $320,000
Amendment $320,000
Original award $320,000

Subawards

Subrecipient Amount Awarded
ST. Mary's College Of Maryland Does lead (Pb) poisoning impair brain development by affecting how thyroid hormone gets into the brain? $199,210

Quick answers

Who received award R01ES035813?

R01ES035813 was awarded to Virginia Polytechnic Institute & State University by National Institute of Environmental Health Sciences (National Institutes of Health) on April 15, 2024.

How much is award R01ES035813 worth?

$960,000 has been obligated on R01ES035813.

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