# MeCP2 Dependent Transcriptional Repression & Neurotransmission

> **NIH NIH R56** · VANDERBILT UNIVERSITY · 2021 · $396,075

## Abstract

PROJECT SUMMARY
Over the past ~15 years, we have examined the role of MeCP2 in neurotransmission as a transcriptional factor
impacting gene expression. Our data has revealed that MeCP2 is a bona fide regulator of synaptic function
with bidirectional changes in MeCP2 resulting in reciprocal alterations in neurotransmission. We have also
shown alterations in MeCP2 expression in mice result in several behavioral phenotypes as well as deficits in
specific measures of synaptic plasticity further implicating MeCP2 as a key mediator of synaptic processes. A
rather surprising finding in the field of depression has been the demonstration that ketamine, an NMDA
receptor antagonist, has rapid and long-lasting antidepressant responses in depressed individuals. We are
investigating the mechanism of the antidepressant action of ketamine, and found that the sustained
antidepressant effects are dependent on MeCP2 Ser421 phosphorylation. In contrast, the rapid
antidepressant action of ketamine is not dependent on MeCP2 Ser421 phosphorylation, revealing a distinct
mechanism between rapid and sustained effects. The objective of this grant is to explore the novel hypothesis
that MeCP2- dependent transcriptional mechanisms underlie the sustained antidepressant effects of ketamine.
We will use state of the art behavioral as well as cellular and biochemical approaches to examine our
hypothesis. Collectively, these studies will contribute to a better understanding of mechanisms underlying the
maintenance of antidepressant effects as well as provide novel insight into MeCP2 regulation as a therapeutic
target.

## Key facts

- **NIH application ID:** 10462209
- **Project number:** 2R56MH081060-12A1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** LISA M MONTEGGIA
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $396,075
- **Award type:** 2
- **Project period:** 2008-04-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10462209

## Citation

> US National Institutes of Health, RePORTER application 10462209, MeCP2 Dependent Transcriptional Repression & Neurotransmission (2R56MH081060-12A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10462209. Licensed CC0.

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