# Inflammatory regulation of neurotrophin signaling in epileptogenesis

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2020 · $332,500

## Abstract

PROJECT SUMMARY
Epilepsy is a common neurological disorder that afflicts about 1% of the population. Although seizures can be
partially controlled by current medications, there is no US FDA-approved drug that can provide disease
prevention or modification despite remarkable advances in epilepsy treatment over the past decades. A major
obstacle to finding such an antiepileptogenic drug is that the molecular mechanisms by which a normal brain is
transformed to generate epileptic seizures remain unsolved. Accumulating evidence from recent clinical and
preclinical studies suggests that the abnormal activation of the brain-derived neurotrophic factor (BDNF)
receptor TrkB (tropomyosin-related kinase receptor B) and its downstream effector phospholipase Cγ1 (PLCγ1)
is sufficient to produce epilepsy following status epilepticus (SE). As TrkB and PLCγ1 are emerging as
attractive molecular targets to prevent acquired epilepsy, a key unsolved puzzle is the signaling events that are
triggered by SE and cause the irregular BDNF/TrkA activity in the hippocampus, thereby leading to
epileptogenesis. In preliminary studies we have demonstrated that the seizure-induced hippocampal
BDNF/TrkB abnormality is largely suppressed by blocking prostaglandin E2 (PGE2) synthesis or signaling. Our
main hypothesis is that PGE2 via a Gαs-dependent signaling pathway upregulates hippocampal BDNF/TrkB
activity and contributes to epileptogenesis following prolonged seizures. Our general approach is to use
biochemical, pharmacological, genetic tools, and multiple in vitro and in vivo model systems to test a
hypothesis that PGE2 is involved in the hippocampal BDNF induction and TrkB activation after SE, to
determine whether seizure-mediated BDNF/TrkB activity involves cAMP/PKA signaling and which Gαs-coupled
PGE2 receptor is engaged, and to determine whether PGE2 signaling via its Gαs-coupled receptors plays a
dominant role in the development of epilepsy and/or the associated behavioral comorbidities after SE.
Successful completion of this project might lead to the discovery of novel molecular targets for the prevention
strategies of acquired epilepsy.

## Key facts

- **NIH application ID:** 9846247
- **Project number:** 5R01NS100947-04
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Jianxiong Jiang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $332,500
- **Award type:** 5
- **Project period:** 2018-08-03 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9846247

## Citation

> US National Institutes of Health, RePORTER application 9846247, Inflammatory regulation of neurotrophin signaling in epileptogenesis (5R01NS100947-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9846247. Licensed CC0.

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