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Mechanistic inquiry of GPR68-mediated neuroprotection against post-stroke deficits and VCID

Award Number: R01NS135594
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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Mechanistic inquiry of GPR68-mediated neuroprotection against post-stroke deficits and VCID - ABSTRACT Stroke leads to acute brain injury and is one of the leading causes of long-term disabilities, which include the development of vascular cognitive impairment (VCI) and post-stroke dementia. Defining new neuroprotective mechanisms following stroke is essential for alleviating both neuronal injury at acute stage and for protecting against post-stroke VCI and dementia. The most common type of stroke in human patients is ischemic stroke. During ischemia or following reperfusion, brain acidification occurs. Acidosis can have both pro-injury and protective effects. In our previous studies, we found that GPR68, also known as ovarian cancer G protein coupled receptor 1 (OGR1), a proton-sensitive G protein coupled receptor (GPCR), is widely expressed in the brain and mediates acid-induced signaling in brain neurons. Our data further suggest that GPR68 activation protects neurons in acidotic and ischemic conditions. To further our knowledge on GPR68-dependent protection, this application will investigate the molecular mechanism by which GPR68 elicits neuroprotection. Using in vitro and in vivo models, we will determine a novel mechanism by which GPR68 induces unfolded protein response (UPR) in neurons. Further, we will assess the translational potential of pharmacological targeting of GPR68. We will perform long-term behavioral assessment to determine whether GPR68 potentiation offers protection against the development of post-stroke disabilities, including post-stroke VCID. Results obtained from the proposed study will uncover novel protective mechanisms mediating GPR68-mediate neuroprotection and generate critical information for novel therapeutic approaches through targeting GPR68 to alleviate post-stroke dementia.


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 = -$1,590 )
2025	2023	THE CURATORS OF THE UNIVERSITY OF MISSOURI	118 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/15/2025	NEW	-$520,000
2025	2023	THE ADMINISTRATORS OF TULANE EDUCATIONAL FUND	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	4/15/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$518,410
														Subtotal = -$1,590

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	THE CURATORS OF THE UNIVERSITY OF MISSOURI	118 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/17/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $627,079 )
2023	2023	UNIVERSITY OF MISSOURI SYSTEM	1011 E 51ST ST	KANSAS CITY	MO	64110	JACKSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/22/2023	NEW	$627,079
														Subtotal = $627,079

Grand Total All Awards = $625,489

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Mechanistic inquiry of GPR68-mediated neuroprotection against post-stroke deficits and VCID

Award Number: R01NS135594

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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