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Assessment of the joint influence of methylmercury and selenium upon postnatal brain development and risk for psychiatric disorders

Award Number: R01ES035851
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/09/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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Assessment of the joint influence of methylmercury and selenium upon postnatal brain development and risk for psychiatric disorders - PROJECT SUMMARY/ABSTRACT Mercury (Hg) is a known neurotoxin considered among the top ten chemicals of public health concern by the World Health Organization. While the acute effects of Hg are well chronicled, the consequences of chronic, low-dose exposure are less clear. Given that clinical symptoms of most psychiatric disorders do not emerge until early adulthood, there is a critical need for better understanding of the neural cell types and circuits most adversely impacted by adolescent Hg exposure, as well as the associated behavioral phenotypes. At the molecular level, Hg irreversibly binds to catalytic selenium (Se) moieties present in antioxidant selenoenzymes, leading to redox dysregulation, altered Ca2+ homeostasis, and mitochondrial dysfunction. Growing evidence indicates that oxidative stress impedes maturation of GABAergic circuitry, resulting in a permanent imbalance between excitatory and inhibitory neurotransmission. Moreover, among GABAergic cell types, fast-spiking, parvalbumin-expressing interneurons (PVIs) are most acutely impacted by redox imbalance. The long-term goal of this project is to better understand how interactions between Hg exposure and dietary Se status influence maturation of excitatory-inhibitory balance and the risk of developing psychiatric disorders. Our central hypothesis is that Hg-mediated inhibition of selenoenzyme activity during adolescence preferentially impairs PVIs, leading to irreversible deficits in excitatory-inhibitory tone and behavior. Our research team has expertise to definitively assess the effects of altered Se metabolism on molecular, immunohistological, and behavioral indices in rodents, with innovative tools and assays established to successfully perform the proposed studies. Our two specific aims are as follows: Aim #1: Determine the effects of Hg on Se-dependent redox balance, excitatory-inhibitory tone, and electrophysiological activity in primary cortical cultures. Aim #2: Characterize the immediate and long-term effects of subtoxic juvenile Hg exposure on brain, behavior, and gut microbiota.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $391,249 )
2026	2026	UNIVERSITY OF HAWAII	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Environmental Health	000	3	2/19/2026	NON-COMPETING CONTINUATION	$391,249
														Subtotal = $391,249

Issue Date FY: 2025 ( Subtotal = $391,538 )
2025	2025	UNIVERSITY OF HAWAII	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Environmental Health	000	2	12/27/2024	NON-COMPETING CONTINUATION	$391,538
														Subtotal = $391,538

Issue Date FY: 2024 ( Subtotal = $405,086 )
2024	2024	UNIVERSITY OF HAWAII	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Environmental Health	000	1	2/9/2024	NEW	$405,086
														Subtotal = $405,086

Grand Total All Awards = $1,187,873

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Assessment of the joint influence of methylmercury and selenium upon postnatal brain development and risk for psychiatric disorders

Award Number: R01ES035851

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/09/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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