# Investigating how stress induced changes in maternal serotonin affect offspring development and stress resilience

> **NIH NIH R01** · ROSWELL PARK CANCER INSTITUTE CORP · 2024 · $429,250

## Abstract

PROJECT SUMMARY
Major depressive disorder and other mood disorders are heterogeneous, debilitating illnesses that affect millions
of individuals worldwide. Antidepressants that target the serotonergic system (e.g., SSRIs) remain the most
effective treatment for these disorders and are widely used. However, emerging data show that maternal
antidepressant treatment affects the long-term health and neurodevelopment of offspring through, as yet poorly
understood epigenetic mechanisms. Recent pioneering discoveries from my lab have allowed us to develop the
model organism C. elegans to dissect the molecular mechanisms by which maternal stress, through the
serotonergic system, impacts chromatin in the pre-fertilized oocyte. Notwithstanding the differences between
the C. elegans and mammalian serotonergic systems (5-HT source being neurons, enterochromaffin cells and
maternal placenta in mammals and only neurons in C. elegans), an acute elevation of serotonin levels is a stress
signal in both mammals and C. elegans and acts through conserved receptor-mediated signal transduction
pathways to induce the ancient, conserved transcription factor, HSF1. Our working hypothesis, premised on
preliminary data, is that the stress-induced release of serotonin from maternal neurons in C. elegans enables
HSF1 to recruit chromatin remodeling proteins in a piRNA (21U-RNA)-dependent manner in the germline and
modify chromatin in pre-fertilized oocytes. The result is that threat perception by the mother alters the
development, behavior and physiology of future offspring. In Aim 1, we will identify the neural bases and
signaling mechanisms of the serotonergic defense survival circuit in the parent. In Aim 2, we will identify the
epigenetic changes in pre-fertilized germ cells caused by maternal serotonin, and understand how they impact
offspring neurodevelopment, behavior, and stress resilience.

## Key facts

- **NIH application ID:** 10775776
- **Project number:** 5R01MH126282-04
- **Recipient organization:** ROSWELL PARK CANCER INSTITUTE CORP
- **Principal Investigator:** Veena Prahlad
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $429,250
- **Award type:** 5
- **Project period:** 2022-04-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10775776

## Citation

> US National Institutes of Health, RePORTER application 10775776, Investigating how stress induced changes in maternal serotonin affect offspring development and stress resilience (5R01MH126282-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10775776. Licensed CC0.

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