Friday, April 26, 2024 4/26/2024

Endocannabinoids in Neurodegenerative Diseases

Award Number: R01NS076815
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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Summary While the etiology of Alzheimer's disease (AD) is multifactorial and complex, results from epidemiological, clinical, and laboratory animal studies implicate traumatic brain injury (TBI) as an important risk factor for AD and dementia. However, the mechanisms by which TBI increases the risk of AD are largely unknown. In particular, there are no effective therapies to prevent or treat TBI-caused AD neuropathology and dementia. Accumulating evidence suggests that neuroinflammation following the primary injury plays a critical factor in secondary brain damage and subsequent neuropathological changes. Therefore, resolving neuroinflammation will significantly reduce secondary brain damage and eventually prevent or reduce the incidence of TBI- induced AD-like neurodegenerative disease. Endogenous cannabinoids display anti-inflammatory and neuroprotective properties. During the current period of funding, we provided evidence that monoacylglycerol lipase (MAGL), the key enzyme that metabolizes the endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain, is likely a new therapeutic target for AD. Pharmacological inactivation of MAGL reduces neuropathology and improves synaptic plasticity and memory formation in animal models of both TBI and AD. However, we do not know whether genetic disruption of MAGL will yield beneficial effects similar to those following pharmacological inhibition of MAGL in TBI. In addition, there is a gap in our knowledge about the signaling pathways that mediate anti-inflammatory and neuroprotective effects produced by MAGL inhibition in TBI. In this competing renewal application, we propose to test our hypothesis that alleviation of TBI-induced AD-like neuropathological changes by pharmacological or genetic disruption of MAGL is primarily mediated by enhancement of 2-AG signaling in astrocytes, which, in turn curbs neuroinflammation. Thus, the primary objective of the studies proposed in this application will use our established mouse model of repetitive mild closed head injury to demonstrate that inhibition of 2-AG metabolism by pharmacological inhibition or genetic disruption of MAGL ameliorates AD-like neuropathology, improves recovery of synaptic and cognitive functions, and halts disease progression and delineate the signaling pathways that mediate the beneficial effects produced by MAGL inhibition. The results from this project may ultimately lead to development of a novel therapeutic intervention for TBI-induced AD-like neurodegenerative 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 = -$55,439 )
2024	2022	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	1/19/2024	NON-COMPETING CONTINUATION	-$55,439
														Subtotal = -$55,439

Issue Date FY: 2022 ( Subtotal = $387,500 )
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	4/14/2022	NON-COMPETING CONTINUATION	$387,500
2022	2018	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER-NEW ORLEANS	433 BOLIVAR ST STE 815	NEW ORLEANS	LA	70112	ORLEANS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	9/26/2022	COMPETING CONTINUATION	$0
														Subtotal = $387,500

Issue Date FY: 2021 ( Subtotal = $386,665 )
2021	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	4/26/2021	NON-COMPETING CONTINUATION	$386,665
														Subtotal = $386,665

Issue Date FY: 2020 ( Subtotal = $385,000 )
2020	2020	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	5/8/2020	NON-COMPETING CONTINUATION	$385,000
														Subtotal = $385,000

Issue Date FY: 2019 ( Subtotal = $381,680 )
2019	2019	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	8	5/31/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$381,250
2019	2019	LOUISIANA STATE UNIVERSITY SYSTEM	433 BOLIVAR ST STE 815	NEW ORLEANS	LA	70112	ORLEANS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	4/19/2019	NON-COMPETING CONTINUATION	$367,500
2019	2019	LOUISIANA STATE UNIVERSITY SYSTEM	433 BOLIVAR ST STE 815	NEW ORLEANS	LA	70112	ORLEANS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	7	6/6/2019	NON-COMPETING CONTINUATION	-$367,500
2019	2019	LOUISIANA STATE UNIVERSITY SYSTEM	433 BOLIVAR ST STE 815	NEW ORLEANS	LA	70112	ORLEANS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	7	5/31/2019	NON-COMPETING CONTINUATION	$0
2019	2019	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	005	8	7/24/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2019	2019	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	008	8	9/5/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$181,184
2019	2019	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	8	6/6/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2019	2018	LOUISIANA STATE UNIVERSITY SYSTEM	433 BOLIVAR ST STE 815	NEW ORLEANS	LA	70112	ORLEANS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	006	6	9/4/2019	COMPETING CONTINUATION	$430
2019	2018	LOUISIANA STATE UNIVERSITY SYSTEM	433 BOLIVAR ST STE 815	NEW ORLEANS	LA	70112	ORLEANS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	007	6	9/5/2019	COMPETING CONTINUATION	-$181,184
														Subtotal = $381,680

Issue Date FY: 2018 ( Subtotal = $367,070 )
2018	2018	LOUISIANA STATE UNIVERSITY SYSTEM	433 BOLIVAR ST STE 815	NEW ORLEANS	LA	70112	ORLEANS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	7/13/2018	COMPETING CONTINUATION	$367,500
2018	2016	LOUISIANA STATE UNIVERSITY SYSTEM	433 BOLIVAR ST STE 815	NEW ORLEANS	LA	70112	ORLEANS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	5/21/2018	SUPPLEMENT FOR EXPANSION	-$430
														Subtotal = $367,070

Issue Date FY: 2016 ( Subtotal = $324,680 )
2016	2016	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	9/21/2016	SUPPLEMENT FOR EXPANSION	$9,680
2016	2016	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	4/4/2016	EXTENSION WITH OR WITHOUT FUNDS	$315,000
														Subtotal = $324,680

Issue Date FY: 2015 ( Subtotal = $315,000 )
2015	2015	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	4/3/2015	NON-COMPETING CONTINUATION	$315,000
														Subtotal = $315,000

Issue Date FY: 2014 ( Subtotal = $311,851 )
2014	2014	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	3/17/2014	NON-COMPETING CONTINUATION	$311,851
														Subtotal = $311,851

Issue Date FY: 2013 ( Subtotal = $353,701 )
2013	2013	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	5/24/2013	NON-COMPETING CONTINUATION	$20,475
2013	2013	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	5/14/2013	SUPPLEMENT FOR EXPANSION	$49,726
2013	2013	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	3/5/2013	NON-COMPETING CONTINUATION	$283,500
														Subtotal = $353,701

Issue Date FY: 2012 ( Subtotal = $315,000 )
2012	2012	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/7/2012	NEW	$310,625
2012	2012	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	6/26/2012	NEW	$4,375
														Subtotal = $315,000

Grand Total All Awards = $3,472,708

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Endocannabinoids in Neurodegenerative Diseases

Award Number: R01NS076815

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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