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

> **NIH NIH K00** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $77,859

## Abstract

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.

## Key facts

- **NIH application ID:** 10918254
- **Project number:** 5K00NS129125-03
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Maria Aisha Jones-Muhammad
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $77,859
- **Award type:** 5
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10918254

## Citation

> US National Institutes of Health, RePORTER application 10918254, Sex-specific development of seizure activity following endocannabinoid system manipulation in the fetal brain (5K00NS129125-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10918254. Licensed CC0.

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