Prenatal stress selectively enhances locomotor hyperactivity in male mice with embryonic loss of Fgfr2

Michelle X. Chen; Polona Jager; Abigail Sawyer; Hanna E. Stevens

doi:10.3389/fpsyt.2026.1820942

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Prenatal stress selectively enhances locomotor hyperactivity in male mice with embryonic loss of Fgfr2

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Prenatal stress selectively enhances locomotor hyperactivity in male mice with embryonic loss of Fgfr2

Michelle X. Chen, Polona Jager, Abigail Sawyer and Hanna E. Stevens

Frontiers in psychiatry, Vol.17, 1820942

09/03/2026

DOI: 10.3389/fpsyt.2026.1820942

PMCID: PMC13584961

PMID: 42757257

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Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a developmental psychiatric disorder associated with a complex interplay of genetic and environmental risk factors. In a previous study, we found embryonic dorsal forebrain loss in male mice of fibroblast growth factor receptor 2 ( Fgfr2 ), which has a critical role in normal brain development, results in ADHD-relevant phenotypes: increased locomotion and sociability, and impaired working memory postnatally. How such genetic vulnerabilities interact with environmental exposures to translationally model human ADHD risk remains unclear. Here, we performed a follow-up study by pairing the embryonic hGFAP-cre Fgfr2 conditional knockout ( Fgfr2 cKO) mouse model with prenatal repetitive restraint stress, modeling an environmental factor associated with ADHD risk, to assess adult offspring behaviors, dopamine transporter (DAT) levels, and pilot parvalbumin-positive (PV+) cell densities. Offspring of prenatally stressed, Fgfr2 cKO male mice showed increased locomotion (80% higher compared to non-stressed, Fgfr2 cKO animals). However, prenatal stress had no significant effects on impulsivity, working memory, or sociability in Fgfr2 cKO male mice. Neurobiologically, prenatal stress did not significantly affect DAT levels, and DAT protein levels did not correlate with behavior, suggesting DAT dysregulation is not the mechanism of increased locomotion in this model. Taken together, our findings implicate prenatal stress as a potential contributor to some gene-environment interactions for ADHD risk, supporting its use in translational animal models of childhood psychiatric disorders.

ADHD

fibroblast growth factor receptor 2 (FGFR2)

gene-environment interaction

neurodevelopment

prenatal stress

Details

Title: Subtitle: Prenatal stress selectively enhances locomotor hyperactivity in male mice with embryonic loss of Fgfr2
Creators: Michelle X. Chen - Carver Bible College
Polona Jager - Yale University
Abigail Sawyer - Yale University
Hanna E. Stevens - Yale University
Resource Type: Journal article
Publication Details: Frontiers in psychiatry, Vol.17, 1820942
DOI: 10.3389/fpsyt.2026.1820942
PMID: 42757257
PMCID: PMC13584961
NLM abbreviation: Front Psychiatry
ISSN: 1664-0640
eISSN: 1664-0640
Publisher: Frontiers Media SA
Grant note: NARSAD/Brain Behavior Research Foundation Young Investigator Award NINDS: T32NS007124 NIMH: K08MH086812 NIEHS: R01ES035696 University of Iowa Ida P Haller Chair in Child and Adolescent Psychiatry (HES)
The author(s) declared that financial support was received for this work and/or its publication. NARSAD/Brain Behavior Research Foundation Young Investigator Award (HES), NINDS grant T32NS007124 (MXC), NIMH grant K08MH086812 (HES), NIEHS grant R01ES035696 (HES), University of Iowa Ida P Haller Chair in Child and Adolescent Psychiatry (HES).
Language: English
Date published: 09/03/2026
Academic Unit: Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9985224447302771

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