# Epigenetics of Regeneration

> **NIH NIH P20** · UNIVERSITY OF NORTH DAKOTA · 2020 · $206,072

## Abstract

Epigenetics of regeneration in the aging brain
PROJECT SUMMARY
This project is designed to investigate the maturational decline in regenerative capability in the rat central nervous
system. Our working hypothesis is that the intrinsic capacity for axon or dendritic regeneration results from an
age-related alteration of epigenetic factors that regulate the organization of chromatin and accessibility of genes
associated with neuronal survival and process outgrowth. This study will directly link altered transcriptome and
acetylation and methylation enzymatic activity with axotomy and collateral axonal sprouting in vivo. Furthermore,
we will provide the first evidence for the maturation-induced changes in the epigenetic landscape that lead to
loss of neuronal plasticity in vivo. Our long term goal is to reverse age-induced alterations in the epigenetic
landscape to promote neuronal survival and process outgrowth in the mature mammalian CNS. Reversal of
maturation associated inhibition of regeneration will provide an important tool for promoting, regulating and
directing a functionally relevant regeneration event in humans following traumatic brain injury, ischemia or
neurodegenerative disease. The principle goals of this project are as follows:
Aim 1: We will use an unbiased approach to compare the transcriptome and epigenomic profile in young
regenerating vs aged non-regenerating hypothalamic neurons
Aim 2: We will test how CNTF-induced JAK/STAT3 signaling triggers epigenetic and transcriptional
events to mediate neuronal survival and axonal outgrowth.
Aim 3: To determine how the PI3K-AKT pathway mediates CNTF-induced process outgrowth.
In addition to applying a novel and highly relevant model system to the study of maturational changes in the
SON neural and astrocyte epigenome, we propose to utilize new and innovative methods to address our
specific objectives. We will take advantage of laser capture microdissection to directly assess the methylation
and acetylation status of young versus mature and sprouting versus non sprouting neurons and astrocytes
isolated from SON in situ. We will also interpret this data in conjunction with analysis of alterations in enzymatic
activity of specific Dnmts, 5-mC hydroxylase TET activity, histone acetyltransferase, histone de-acetyltransferase
and histone methyltransferase in isolated SON under similar experimental conditions.

## Key facts

- **NIH application ID:** 9976555
- **Project number:** 5P20GM104360-07
- **Recipient organization:** UNIVERSITY OF NORTH DAKOTA
- **Principal Investigator:** John Andrew Watt
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $206,072
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976555

## Citation

> US National Institutes of Health, RePORTER application 9976555, Epigenetics of Regeneration (5P20GM104360-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9976555. Licensed CC0.

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