# Role of Mecp2 in rapidly acting antidepressant action.

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2024 · $596,783

## Abstract

PROJECT SUMMARY
The objective of this application is to investigate the role of MeCP2 in the sustained
antidepressant action of ketamine. Studies from our laboratory, as well as others, demonstrate
that MeCP2 is a strong regulator of synaptic function with bidirectional changes in MeCP2
expression producing reciprocal alterations in neurotransmission. Studies have been examining
how intracellular signaling mechanisms produce the acute antidepressant action of ketamine
and transition to a sustained effect that may last over a week. This sustained ketamine effects
requires the function of Methyl-CpG binding protein 2 (MeCP2), specifically MeCP2 Ser421
phosphorylation. We propose experiments to identify the mechanisms by which acute ketamine
administration elicits MeCP2 phosphorylation at Ser421 and how this event is required for the
sustained, but not the rapid effects of ketamine. A mechanistic understanding of the sustained
effects of ketamine, and the underlying neurobiology, provide possible avenues to prolong
antidepressant action and thus reduce the frequency of ketamine administration and potential
adverse effects.

## Key facts

- **NIH application ID:** 10872917
- **Project number:** 1R01MH136569-01
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** LISA M MONTEGGIA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $596,783
- **Award type:** 1
- **Project period:** 2024-03-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10872917

## Citation

> US National Institutes of Health, RePORTER application 10872917, Role of Mecp2 in rapidly acting antidepressant action. (1R01MH136569-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10872917. Licensed CC0.

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