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Homeostatic control of the NMDA receptor co-agonist D-serine by SLC1A4

Award Number: R01MH110646
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/17/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2023

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Homeostatic control of the NMDA receptor co-agonist D-serine by SLC1A4 - NMDA receptors (NMDARs) participate in processes ranging from neural development to learning and memory. Disorders of NMDAR signaling are linked to several neurological diseases. Accumulating evidence suggests that the endogenous co-agonist D-serine plays a prominent role in activation of synaptic NMDARs in cortex. However, there are significant gaps in our understanding of the physiological mechanisms involved in D-serine homeostasis in brain and their potential impact on NMDAR signaling. Our preliminary data suggest that SLC1A4, a neutral amino acid transporter paralog within the SLC1 solute carrier family that includes glutamate transporters, unexpectedly mediates transmembrane flux of D-serine. We will test the hypotheses that SLC1A4 is in fact the major route of sodium-dependent D-serine uptake in brain and that selective SLC1A4 inhibitors developed from a hydroxyproline pharmacophore can alter D-serine homeostasis and thereby modulate NMDAR function and synaptic plasticity. We will also characterize the structure and function of a recently identified mutation in the human gene encoding SLC1A4 that is linked to neurodevelopmental and cognitive deficits, and we will create and study a transgenic mouse model of this human disease.


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: 2024 ( Subtotal = -$2,715 )
2024	2022	THE MCLAUGHLIN RESEARCH INSTITUTE FOR BIOMEDICAL SCIENCES, INC.	1520 23RD ST S	GREAT FALLS	MT	59405	CASCADE	USA	Mental Health Research Grants	000	5	2/16/2024	NON-COMPETING CONTINUATION	-$2,715
														Subtotal = -$2,715

Issue Date FY: 2022 ( Subtotal = $405,000 )
2022	2022	MCLAUGHLIN RESEARCH INSTITUTE FOR BIOMEDICAL SCIENCES, INC., THE	1520 23RD ST S	GREAT FALLS	MT	59405	CASCADE	USA	Mental Health Research Grants	000	5	3/17/2022	NON-COMPETING CONTINUATION	$405,000
														Subtotal = $405,000

Issue Date FY: 2021 ( Subtotal = $405,000 )
2021	2021	MCLAUGHLIN RESEARCH INSTITUTE FOR BIOMEDICAL SCIENCES, INC., THE	1520 23RD ST S	GREAT FALLS	MT	59405	CASCADE	USA	Mental Health Research Grants	000	4	3/5/2021	NON-COMPETING CONTINUATION	$405,000
														Subtotal = $405,000

Issue Date FY: 2020 ( Subtotal = $405,000 )
2020	2020	MCLAUGHLIN RESEARCH INSTITUTE FOR BIOMEDICAL SCIENCES, INC., THE	1520 23RD ST S	GREAT FALLS	MT	59405	CASCADE	USA	Mental Health Research Grants	000	3	3/12/2020	NON-COMPETING CONTINUATION	$405,000
														Subtotal = $405,000

Issue Date FY: 2019 ( Subtotal = $405,000 )
2019	2019	MCLAUGHLIN RESEARCH INSTITUTE FOR BIOMEDICAL SCIENCES, INC., THE	1520 23RD ST S	GREAT FALLS	MT	59405	CASCADE	USA	Mental Health Research Grants	000	2	3/9/2019	NON-COMPETING CONTINUATION	$405,000
														Subtotal = $405,000

Issue Date FY: 2018 ( Subtotal = $405,000 )
2018	2018	MCLAUGHLIN RESEARCH INSTITUTE FOR BIOMEDICAL SCIENCES, INC., THE	1520 23RD ST S	GREAT FALLS	MT	59405	CASCADE	USA	Mental Health Research Grants	000	1	2/21/2018	NEW	$405,000
														Subtotal = $405,000

Grand Total All Awards = $2,022,285

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Homeostatic control of the NMDA receptor co-agonist D-serine by SLC1A4

Award Number: R01MH110646

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/17/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2023

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