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Stabilizing the Tripartite Synaptic Complex Following TBI

Award Number: R01NS098740
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2017
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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Stabilizing the Tripartite Synaptic Complex Following TBI - Summary: Human consciousness and cognitive function are governed by a complex brain circuitry made up of neural connections regulated by an integrated multicellular network. Glial make up 90% of all cells in the brain and play dynamic and active roles in neuronal signaling, where astrocytes and microglia regulate synaptic transmission and plasticity. In the past decade, increasing evidence suggests that the principal co-agonist for N-methyl-D- Aspartate receptors (NMDARs) is the D-amino acid, D-serine, rather than glycine; however, few studies have examined its role in CNS pathologies. To address this gap, we have recently identified a novel mechanism of synaptic damage, where glia within the tripartite synapse uniquely synthesize and release D-serine following the onset of pathological events. We hypothesize that microglia are a key source of pathological D-serine that hyperactivates extrasynaptic NMDAR subunits to initiate synaptic damage as a result of microglia targeting and pruning of dendritic spines. Our proposed experiments will examine (1) the mechanisms of D-serine release from microglia; (2) the mechanisms of synaptic damage and microglia targeting & pruning; (3) transcriptomic analysis of brain injury in both murine and human models. We will achieve this by employing both genetic and pharmacological approaches to dissect the mechanism of microglial action within the complexity of brain injury using state-of-the-art transcriptomic, imaging, and genetic techniques. Our studies will result in a better understanding of the mechanisms that regulate synaptic damage and dysfunction, but also will start to define novel therapeutics for patient interventions.


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 = $496,567 )
2026	2026	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	1/7/2026	NON-COMPETING CONTINUATION	$446,910
2026	2026	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	9	3/5/2026	NON-COMPETING CONTINUATION	$49,657
														Subtotal = $496,567

Issue Date FY: 2025 ( Subtotal = $504,070 )
2025	2025	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	1/15/2025	NON-COMPETING CONTINUATION	$469,706
2025	2025	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	8	1/16/2025	SUPPLEMENT FOR EXPANSION	$34,364
2025	2021	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	1/15/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $504,070

Issue Date FY: 2024 ( Subtotal = $617,704 )
2024	2024	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	7	6/4/2024	NON-COMPETING CONTINUATION	$38,342
2024	2024	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	7	1/10/2024	SUPPLEMENT FOR EXPANSION	$86,390
2024	2024	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	1/3/2024	NON-COMPETING CONTINUATION	$492,972
														Subtotal = $617,704

Issue Date FY: 2023 ( Subtotal = $618,655 )
2023	2023	UNIVERSITY OF MIAMI	1400 NW 10TH AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	7/6/2023	SUPPLEMENT FOR EXPANSION	$52,214
2023	2023	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	12/21/2022	COMPETING CONTINUATION	$566,441
														Subtotal = $618,655

Issue Date FY: 2021 ( Subtotal = $496,948 )
2021	2021	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	2/3/2021	NON-COMPETING CONTINUATION	$496,948
														Subtotal = $496,948

Issue Date FY: 2020 ( Subtotal = $496,948 )
2020	2020	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	1/22/2020	SUPPLEMENT FOR EXPANSION	$58,728
2020	2020	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	4	2/11/2020	NON-COMPETING CONTINUATION	$43,821
2020	2020	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/18/2019	NON-COMPETING CONTINUATION	$394,399
														Subtotal = $496,948

Issue Date FY: 2019 ( Subtotal = $493,192 )
2019	2019	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	12/18/2018	NON-COMPETING CONTINUATION	$493,192
														Subtotal = $493,192

Issue Date FY: 2018 ( Subtotal = $493,192 )
2018	2018	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	4/25/2018	NON-COMPETING CONTINUATION	$43,821
2018	2018	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/22/2017	NON-COMPETING CONTINUATION	$394,399
2018	2018	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	12/27/2017	SUPPLEMENT FOR EXPANSION	$54,972
														Subtotal = $493,192

Issue Date FY: 2017 ( Subtotal = $475,106 )
2017	2017	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	1/26/2017	NEW	$475,106
														Subtotal = $475,106

Grand Total All Awards = $4,692,382

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Stabilizing the Tripartite Synaptic Complex Following TBI

Award Number: R01NS098740

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2017

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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