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Transfer request of grant 1R21MH119561-01A1 (Deslauriers, Jessica) to Laval University

Award Number: R21MH119561
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2020
PERIOD OF PERFORMANCE END DATE: 12/31/2022

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Transfer request of grant 1R21MH119561-01A1 (Deslauriers, Jessica) to Laval University - There is an increased cardiovascular risk in individuals with posttraumatic stress disorder (PTSD). However, the causal relationship between cardiovascular risk/hypertension and PTSD remains unclear, and the mechanisms underlying the high comorbidity of PTSD with cardiovascular diseases are not well understood. Evidence suggests that the actions of commonly used blood pressure medications that target the renin- angiotensin system extend beyond blood pressure reduction and may have therapeutic effects on trauma- related disorders, such as PTSD. The mechanisms for how angiotensin II (Ang II) signaling through Ang-II type 1 receptors (AT1R) affects trauma response and symptoms are not clear. Ang-II is released during severe stress, and there is some evidence for central AT1aRs to potentially affect PTSD through direct effects on fear circuit activation. An alternate mechanism however is that peripheral Ang II signaling may also contribute to development of PTSD through exposure of the central nervous system to inflammatory signaling via disruption of the blood brain barrier (BBB) during and after trauma. The BBB, by being the primary barrier separating the peripheral and central systems, is crucial in the regulation of central homeostasis. BBB integrity is disrupted by hypertension and severe stress, and is associated with one of the strongest trauma-related risk factors for PTSD, traumatic brain injury. AT1R activation of Gq signaling disrupts the tight junctions of endothelial cells, allowing larger molecules such as proteins to pass through. Here we propose that severe stress increases peripheral Ang II, which activates endothelial AT1Rs, leading to both increased blood pressure and BBB permeability. The trauma-induced BBB breakdown may then enable access of peripheral inflammatory signaling molecules to the brain, increasing the risk for PTSD. We propose to test this hypothesis by using cell- type specific genetic and chemogenic tools to probe the contribution of peripheral AT1aR signaling to enduring central inflammatory and behavioral responses to trauma. Aim 1 will test the hypothesis that peripheral AT1aR signaling is necessary for trauma-induced increases in enduring central inflammation PTSD-like behavior. Aim 2 will test the hypothesis that Gq/11 signaling in endothelial cells during and after trauma is sufficient to disrupt BBB integrity and increase enduring inflammatory and behavioral responses to trauma. Thus, the proposed studies will identify the relationship between peripheral and central renin-angiotensin system to lead to increased central immune signaling and enduring trauma symptoms, and provide insights into the contribution of BBB permeability to trauma risk and symptom maintenance.


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 = $0 )
2024	2021	UNIVERSITE LAVAL	2345 ALLEE DES BIBLIOTHEQUES	QUEBEC	QC			CAN	Mental Health Research Grants	000	3	10/17/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $135,000 )
2021	2021	UNIVERSITE LAVAL	2345 ALLE DES BIBLIOTHEQUES	QUEBEC	QC			CAN	Mental Health Research Grants	001	3	6/18/2021	NON-COMPETING CONTINUATION	$135,000
2021	2020	UNIVERSITE LAVAL	2345 ALLE DES BIBLIOTHEQUES	QUEBEC	QC			CAN	Mental Health Research Grants	000	2	1/29/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $135,000

Issue Date FY: 2020 ( Subtotal = $161,206 )
2020	2020	UNIVERSITE LAVAL	2345 ALLE DES BIBLIOTHEQUES	QUEBEC	QC	G1V 0A6		CAN	Mental Health Research Grants	002	2	6/30/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$161,206
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	003	1	9/3/2020	NEW	$0
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	001	1	6/30/2020	NEW	-$236,250
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	000	1	12/14/2019	NEW	$236,250
														Subtotal = $161,206

Grand Total All Awards = $296,206

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Transfer request of grant 1R21MH119561-01A1 (Deslauriers, Jessica) to Laval University

Award Number: R21MH119561

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2020

PERIOD OF PERFORMANCE END DATE: 12/31/2022

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