# Role of Notch signaling in regulating post-TBI neurogenesis and plasticity

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2021 · $379,419

## Abstract

It is now well established that the mature brain is capable of mounting a reparative response as neural
stem cells (NSCs) within the neurogenic regions of the brain, the subventricular zone and the hippocampus,
proliferate and generate functional neurons under homeostatic condition and following brain insults. However,
the regenerative potential of NSCs is diminished with aging. Thus far, the regulatory mechanisms which drive
activation of regenerative NSCs during neuropathological conditions particularly following TBI is largely
unknown. Furthermore, it is also unclear whether there is an age-related difference in regulating regenerative
NSC response following brain injury. Developmental studies have established that Notch signaling pathway is
essential for NSC maintenance, proliferation and survival during CNS development. Recent studies have also
shown that Notch signaling is a key player for NSCs in the adult brain under homeostatic condition. As the
injured brain recapitulates many aspects as the developing brain, we speculate that Notch signaling is likely
the key regulator responsible for the activation and function of regenerative NSCs following brain injury and
aging. In our preliminary studies, we have found that following brain injury, the expression level of Notch
pathway proteins is elevated in the neurogenic regions in young adult brain which is correlated to the increased
NSC proliferation and neurogenesis. In contrast, in the aged brain, the neurogenic regions display diminished
expression of Notch pathway in normal condition and following TBI which parallels to the decreased NSC
response in the aging brain. From these observations, we hypothesize that Notch signaling is necessary for
activation of regenerative NSCs in the injured brain and reduced Notch signaling during aging contributes to
the decreased regenerative response of NSCs in the aged brain following injury. To test this hypothesis, in
Aim 1 of this proposal, we will determine the importance of Notch signaling in regenerative NSC response and
functional recovery after TBI. In Aim 2, we will assess the significance of Notch signaling on regenerative
NSCs on cellular learning, memory and plasticity in the hippocampus and olfactory bulb following TBI. In Aim
3, we will examine how Notch pathway activation in neurogenic niches affects the function of regenerative
NSCs in the injured aged brain. As the significance of endogenous repair mechanism through NSCs in the
adult brain is increasingly recognized and has attracted increasing interests for development of NSC-based
therapies, it is necessary to understand the fundamental principles governing NSC activation under
regenerative conditions. The goal of this proposal is to examine the regulatory signaling pathway responsible
for regenerative NSC activation and functioning following TBI and aging with the focus on the role of Notch.
.

## Key facts

- **NIH application ID:** 10098076
- **Project number:** 5R01NS101955-05
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Dong Sun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $379,419
- **Award type:** 5
- **Project period:** 2017-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10098076

## Citation

> US National Institutes of Health, RePORTER application 10098076, Role of Notch signaling in regulating post-TBI neurogenesis and plasticity (5R01NS101955-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10098076. Licensed CC0.

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