# Molecular control of aberrant adult-born granule cells in epilepsy.

> **NIH NIH R01** · UNIVERSITY OF TEXAS SAN ANTONIO · 2024 · $25,569

## Abstract

PROJECT SUMMARY/ABSTRACT
The latent period after a severe brain insult such as traumatic brain injury or status epilepticus, and before the
onset of spontaneous recurrent seizures, is characterized by changes in adult hippocampal neurogenesis.
Profound morphological changes, including hilar ectopic granule cells and abnormal dendritic development (e.g.,
hilar basal dendrites) is observed, therefore raising the question whether seizure- induced neurogenesis is
epileptogenic. Our past work of ablating adult neurogenesis before or after acute seizures has shown a pro-
epileptic role of new neurons, however existing ablation strategies in animal models have all suffered from an
inability to decipher the mechanisms that promote aberrant adult-born granule cells (abGCs) because the cells
are removed from the circuit. In this supplement, we will capitalize on recently published work from our laboratory
demonstrating that activity in immature abGCs regulates Ca2+ and gene expression which is necessary and
sufficient for the production of aberrant abGCs and disruption of the hippocampal circuitry leading to epilepsy.
We propose work to determine the mechanisms that promote aberrant neurogenesis, focusing on the genes and
signaling pathways that drive aberrant abGCs as well as identifying the neuronal inputs to the aberrant abGCs.
In this Diversity Supplement, we will perform new experiments to expand the scope of Aim 1 of the parent R01
application, which is to determine the function of previously identified hM4Di-identified genes in aberrant
neurogenesis and seizure. The proposed project will use human embryonic stem cells (ESCs) and 3D neural
organoids to examine the role of TIMP3, a tissue inhibitor of matrix metalloproteinase, by using a small molecule
to knockdown its expression. These studies are expected to provide a greater understanding of the mechanisms
that promote aberrant neurogenesis, which may offer new strategies to specifically target abnormal new neurons
while sparing healthy ones. These studies would be broadly impactful in a variety of neurological disorders
including epilepsy.

## Key facts

- **NIH application ID:** 11034329
- **Project number:** 3R01NS124855-01A1S1
- **Recipient organization:** UNIVERSITY OF TEXAS SAN ANTONIO
- **Principal Investigator:** Jenny Hsieh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $25,569
- **Award type:** 3
- **Project period:** 2024-04-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11034329

## Citation

> US National Institutes of Health, RePORTER application 11034329, Molecular control of aberrant adult-born granule cells in epilepsy. (3R01NS124855-01A1S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11034329. Licensed CC0.

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