# Regulation of adult hippocampal function by the neural stem and progenitor cell secretome

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2024 · $377,481

## Abstract

A unique neurogenic niche in the adult hippocampus hosts neural-lineage stem cells that can persist throughout
the lifespan in a wide range of adult mammals. Uncovering the functional role of these stem cells and how they
interact with other cell types in the niche can provide insight in to the mechanisms that mediate hippocampal
cognitive-emotional functions, as well as potential mechanisms for regenerating tissue in the adult brain.
Recently, stem cell secreted proteins (i.e. the stem cell secretome) have emerged as influential players in tissue
homeostasis. However, relatively little is known about either the content or the function of the secretome of
endogenous neural stem cells and their progenitors (NSPCs) in the adult hippocampus. Our preliminary data
reveal that adult hippocampal NSPCs may regulate their microenvironment through the production of the soluble
protein, vascular endothelial growth factor (VEGF). We find that NSPCs synthesize large quantities of VEGF in
their hippocampal niche and that NSPC-derived VEGF is necessary for sustaining healthy hippocampal function.
We propose to investigate the hypothesis that NSPCs support hippocampal function by direct actions of VEGF
that suppress neuronal hyperexcitability, ultimately supporting memory function, as well as protecting it from
injury. In Aim 1, we will use RNAsequencing as well as genetic code expansion coupled with biorthogonal non-
canonical amino acid protein tagging to determine the specific local contributions of NSPCs to VEGF isoforms
in the cell layers of the dentate gyrus subregion where these cells reside. In Aim 2, we will use transgenic
knockdown and viral rescue models to investigate how dentate gyrus circuit activity is regulated specifically by
NSPC-derived VEGF. In Aim 3, we will use transgenic knockdown and viral rescue models to determine how
NSPC-VEGF influences hippocampal behavioral functions and vulnerability to excitotoxic injury. The completion
of this work will establish a new functional dimension of endogenous NSPCs via their secretome, and advance
understanding of how hippocampal health is actively maintained in a unique niche of the adult brain.

## Key facts

- **NIH application ID:** 10747869
- **Project number:** 5R01NS124775-03
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Elizabeth Diana Kirby
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $377,481
- **Award type:** 5
- **Project period:** 2021-12-23 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10747869

## Citation

> US National Institutes of Health, RePORTER application 10747869, Regulation of adult hippocampal function by the neural stem and progenitor cell secretome (5R01NS124775-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10747869. Licensed CC0.

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