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Investigating how stress induced changes in maternal serotonin affect offspring development and stress resilience

Award Number: R01MH126282
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Investigating how stress induced changes in maternal serotonin affect offspring development and stress resilience - PROJECT SUMMARY Major depressive disorder and other mood disorders are heterogeneous, debilitating illnesses that affect millions of individuals worldwide. Antidepressants that target the serotonergic system (e.g., SSRIs) remain the most effective treatment for these disorders and are widely used. However, emerging data show that maternal antidepressant treatment affects the long-term health and neurodevelopment of offspring through, as yet poorly understood epigenetic mechanisms. Recent pioneering discoveries from my lab have allowed us to develop the model organism C. elegans to dissect the molecular mechanisms by which maternal stress, through the serotonergic system, impacts chromatin in the pre-fertilized oocyte. Notwithstanding the differences between the C. elegans and mammalian serotonergic systems (5-HT source being neurons, enterochromaffin cells and maternal placenta in mammals and only neurons in C. elegans), an acute elevation of serotonin levels is a stress signal in both mammals and C. elegans and acts through conserved receptor-mediated signal transduction pathways to induce the ancient, conserved transcription factor, HSF1. Our working hypothesis, premised on preliminary data, is that the stress-induced release of serotonin from maternal neurons in C. elegans enables HSF1 to recruit chromatin remodeling proteins in a piRNA (21U-RNA)-dependent manner in the germline and modify chromatin in pre-fertilized oocytes. The result is that threat perception by the mother alters the development, behavior and physiology of future offspring. In Aim 1, we will identify the neural bases and signaling mechanisms of the serotonergic defense survival circuit in the parent. In Aim 2, we will identify the epigenetic changes in pre-fertilized germ cells caused by maternal serotonin, and understand how they impact offspring neurodevelopment, behavior, and stress resilience.


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: 2025 ( Subtotal = $364,862 )
2025	2025	HEALTH RESEARCH, INC.	665 ELM ST	BUFFALO	NY	14203	ERIE	USA	Mental Health Research Grants	000	5	4/28/2025	NON-COMPETING CONTINUATION	$364,862
														Subtotal = $364,862

Issue Date FY: 2024 ( Subtotal = $485,146 )
2024	2024	HEALTH RESEARCH, INC.	665 ELM ST	BUFFALO	NY	14203	ERIE	USA	Mental Health Research Grants	005	4	3/11/2024	NON-COMPETING CONTINUATION	$386,325
2024	2024	HEALTH RESEARCH, INC.	665 ELM ST	BUFFALO	NY	14203	ERIE	USA	Mental Health Research Grants	006	4	8/26/2024	NON-COMPETING CONTINUATION	$42,925
2024	2023	HEALTH RESEARCH, INC.	665 ELM ST	BUFFALO	NY	14203	ERIE	USA	Mental Health Research Grants	004	3	12/12/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$96,628
2024	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Mental Health Research Grants	003	2	12/12/2023	NON-COMPETING CONTINUATION	-$1
2024	2023	HEALTH RESEARCH, INC.	ELM & CARLTON ST	BUFFALO	NY	14263	ERIE	USA	Mental Health Research Grants	001	3	11/9/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$429,250
2024	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Mental Health Research Grants	000	2	11/8/2023	NON-COMPETING CONTINUATION	-$373,354
2024	2022	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Mental Health Research Grants	002	1	12/12/2023	NEW	-$96,627
														Subtotal = $485,146

Issue Date FY: 2023 ( Subtotal = $373,355 )
2023	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Mental Health Research Grants	000	2	2/3/2023	NON-COMPETING CONTINUATION	$373,355
														Subtotal = $373,355

Issue Date FY: 2022 ( Subtotal = $360,105 )
2022	2022	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Mental Health Research Grants	000	1	4/5/2022	NEW	$360,105
														Subtotal = $360,105

Grand Total All Awards = $1,583,468

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Investigating how stress induced changes in maternal serotonin affect offspring development and stress resilience

Award Number: R01MH126282

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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