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Sex-specific development of seizure activity following endocannabinoid system manipulation in the fetal brain

Award Number: K00NS129125
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: 07/01/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Sex-specific development of seizure activity following endocannabinoid system manipulation in the fetal brain - Project Summary Preeclampsia, a hypertensive disorder of pregnancy, can advance to eclampsia, when the mother displays novel seizures. The mechanisms that cause some preeclampsia patients to advance to eclampsia are unknown. The long-term goals are to identify therapeutic targets to prevent seizures in pregnancy and preeclampsia and to pursue a career as an academic scientist. The overall objectives of this application are to: 1) identify whether the endocannabinoid system is involved in increased seizure sensitivity in preclinical model of eclampsia, and 2) provide me the additional training to establish a successful career as an academic scientist. The central hypothesis is that changes in cannabinoid receptor 1 (CB1R) activity is impaired following reduced utero-placental perfusion (RUPP) and that impaired CB1R activation increases seizure severity. The rationale for this project is that the rat RUPP model showed increased seizure susceptibility; however, the contributing factors are not fully known. Additionally, seizures occur when brain activity is not effectively modulated and the endocannabinoid system has been shown to modulate neuronal activity and play a significant role in seizure activity. Our preliminary work shows abnormal expression of enzymes important for endocannabinoid system activity in a mouse RUPP model. Because these enzymes play an important role in modulating CB1R activity, it is possible that the RUPP interferes with the endocannabinoid system’s ability to modulate neuronal activity and thus increases sensitivity to seizures. Aim 1 will determine whether RUPP impairs CB1R activity and whether modulating CB1R activity increases seizure severity following RUPP. My postdoctoral plans in Aim 2 focus on the offspring and will determine whether disrupting the endocannabinoid system during pregnancy leads to sex-specific differences in epilepsy in the adolescent offspring. This application is innovative because it combines a clinically-relevant preclinical model of eclampsia with a well-established neuronal modulator, the endocannabinoids, thus having the potential to identify a novel therapeutic target. This grant will also allow for the continued career development and success of a very promising neuroscientist.


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 = $77,859 )
2026	2026	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	6/26/2026	NON-COMPETING CONTINUATION	$77,859
														Subtotal = $77,859

Issue Date FY: 2025 ( Subtotal = $70,074 )
2025	2025	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	8/7/2025	NON-COMPETING CONTINUATION	$70,074
														Subtotal = $70,074

Issue Date FY: 2024 ( Subtotal = $77,859 )
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	6/27/2024	NON-COMPETING CONTINUATION	$77,859
														Subtotal = $77,859

Issue Date FY: 2023 ( Subtotal = $77,859 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	9/1/2023	EXTENSION WITH OR WITHOUT FUNDS	$77,859
														Subtotal = $77,859

Grand Total All Awards = $303,651

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Sex-specific development of seizure activity following endocannabinoid system manipulation in the fetal brain

Award Number: K00NS129125

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: 07/01/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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