# Examining adult hippocampal neurogenesis and cognitive function in Rett syndrome

> **NIH NIH F32** · BAYLOR COLLEGE OF MEDICINE · 2022 · $67,582

## Abstract

Project Summary
Rett syndrome (RTT) is a progressive neurological disorder caused by loss-of-function mutations in methyl-CpG-
binding protein 2 (MECP2). RTT primarily affects girls and is a frequent cause of X-linked intellectual disability.
There are currently no cures for RTT and no available treatments that improve learning and memory function in
these patients. Mouse models of RTT mutations recapitulate many aspects of the disorder, including impairments
of learning and memory. These animals are critical tools for advancing our understanding of both the basic
biology of RTT syndrome and for testing potential treatments. A breakthrough discovery from the Zoghbi and
Tang labs found that deep brain stimulation in the hippocampus of RTT mice rescued learning and memory
impairments. This stimulation also significantly increased adult hippocampal neurogenesis (AHN), a neural
process strongly linked to memory formation, in RTT mice. Whether stimulating AHN alone can improve cognitive
function in RTT is unknown. MeCP2 is known to regulate important features of the AHN cascade, such as the
proliferation of adult neural stem cells and maturation of adult-born granule neurons. However, the molecular
mechanisms disrupting this process in RTT remain unclear. The goal of my project is to address this conceptual
gap in our understanding of the how MeCP2 regulates AHN and how AHN contributes to cognitive function in
RTT. In my proposal, I focus on two questions: 1) what are the molecular mechanisms disrupting AHN in RTT?
2) Does boosting AHN rescue learning and memory deficits in RTT? I hypothesize that MeCP2 regulates a cell-
type-specific transcriptional program important for adult neurogenesis and that enhancing AHN will improve
learning and memory performance in RTT animals. In Aim 1, I propose to identify key transcriptional changes
during critical stages of AHN by tracking newborn neurons as they develop and using single-nuclei RNA-
sequencing to identify the molecular and cellular differences in control vs RTT mice. In Aim 2, I propose to
increase AHN via stimulation of the TLX-nuclear receptor, a master regulator of hippocampal neurogenesis, in
RTT mice and measure if learning and memory behaviors are rescued. Together, these Aims will help build a
comprehensive understanding of how MeCP2 influences AHN and cognitive behaviors in the context of RTT.
The ultimate goal of these data will be to identify and develop targeted treatment-based strategies to improve
learning and memory function in RTT and potentially other MECP2-related disorders.

## Key facts

- **NIH application ID:** 10425703
- **Project number:** 1F32NS122920-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Ashley Grace Anderson
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,582
- **Award type:** 1
- **Project period:** 2022-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10425703

## Citation

> US National Institutes of Health, RePORTER application 10425703, Examining adult hippocampal neurogenesis and cognitive function in Rett syndrome (1F32NS122920-01A1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10425703. Licensed CC0.

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