# BMP Signaling and Neurogenesis in Major Depressive Order

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $456,079

## Abstract

Summary
Major depressive disorder (MDD) is one of the leading causes of disability and lost productivity.
Nearly half of all clinically depressed patients fail to respond to the first prescribed antidepressant,
and about a third fail to respond to all medications. Development of new approaches will require
better understand of the mechanisms underlying the disorder. This project has identified and is
examining a signaling pathway not previously implicated in anxiety and depression-like behavior,
bone morphogenetic protein (BMP) signaling. MDD is associated with reductions in volume of the
hippocampus (HC) in humans and in neurogenesis in the HC in animal models of the disorder.
Reduction of BMP signaling in the HC in mice is sufficient to produce antidepressant-like changes
in behavior and to increase neurogenesis. Treatment with several different classes of
antidepressant drugs reduces BMP signaling in the HC, and prevention of this reduction in BMP
signaling blocks the effects of the drugs on both behavior and neurogenesis. Inhibition of BMP
signaling in the HC also blocks the effects of unpredictable chronic mild stress on both depression-
like behavior and neurogenesis. Thus BMP signaling in the hippocampus regulates both
depression-like behavior. However, a causal link between the changes in neurogenesis and
behavior has not been established. The proposed studies will determine whether there is a causal
relationship between changes in neurogenesis, electrophysiological activity of newly generated
neurons, and behavior after inhibition of BMP signaling in HC stem/progenitor cells. They also
will define the role of BMP signaling in cellular and behavioral responses to stress, and test the
hypothesis that that gene expression changes due to elevated BMP signaling contribute to the
decrease in neurogenesis, increased proportion of quiescent neural stem cells, and behavioral
changes associated with stress/depression.

## Key facts

- **NIH application ID:** 10094255
- **Project number:** 5R01MH114923-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** JOHN A KESSLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $456,079
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10094255

## Citation

> US National Institutes of Health, RePORTER application 10094255, BMP Signaling and Neurogenesis in Major Depressive Order (5R01MH114923-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10094255. Licensed CC0.

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