Glucocorticoid receptors in oligodendrocyte precursor cells regulate hippocampal network plasticity and stress-induced behavior in mice
Abstract
Glucocorticoid receptors (GRs) are key mediators of how the stress hormone glucocorticoids (GCs) shape postnatal brain development and adaptive plasticity. Because GC signaling is critical during this period, postnatal GC concentrations are tightly regulated in the brain, whereas excessive levels of circulating GCs can disrupt developmental trajectories and increase the risk of psychiatric disorders later in life. GR function influences multiple neural cell types, but its cell-specific roles, particularly early in development, remain poorly understood. Oligodendrocyte precursor cells (OPCs), which generate myelinating oligodendrocytes and actively modulate neuronal networks, express GRs and can therefore respond to fluctuations in GC levels. Although excessive GC exposure during early life adversity has been linked to changes in OPC development, the physiological role of GR signaling specifically within OPCs remains unclear. To address this, we conditionally deleted GRs in postnatal OPCs in mice to investigate the role of physiological GC signaling in OPC proliferation and maturation, as well as in neuronal network activity and behavior. This deletion resulted in reduced oligodendrocyte and myelinated axon density in the hippocampus, sex-specific alterations in hippocampal activity and long-term potentiation following acute challenge, and impairments in memory formation in adulthood. Our findings reveal an OPC-specific role for GRs and suggest that physiological GR activity in the oligodendrocyte lineage contributes to normal hippocampal plasticity, learning, and memory.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (27)
Lorenzo Mattioni
Institute of Anatomy, University Medical Center of the Johannes Gutenberg-University
Giulia Poggi
Institute of Anatomy, University Medical Center of the Johannes Gutenberg-University
Celine Gallagher
Institute of Physiology, University Medical Center of the Johannes Gutenberg-University
Katrin Becker
Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University
Linh Le
Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University
Maja Papic
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University
Jasmin Engbers
Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University
Maija-Kreetta Koskinen
SleepWell Research Program, Faculty of Medicine, University of Helsinki
Ali Abdollahzadeh
A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland
David P. Herzog
Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University
Leonardo Nardi
Institute of Anatomy, University Medical Center of the Johannes Gutenberg-University
Andrea Conrad
Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University
Sarah Winterberg
Department of Systemic Neuroscience, Institute of Anatomy and Cell Biology, Philipps University
Christa Merte-Grebe
Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, Medical Faculty, Philipps University Marburg
Liana Melo-Thomas
Department of Systemic Neuroscience, Institute of Anatomy and Cell Biology, Philipps University
Hyonseung Lee
Department of Systemic Neuroscience, Institute of Anatomy and Cell Biology, Philipps University
Hans Schwarzbach
Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, Medical Faculty, Philipps University Marburg
Jennifer Klüpfel
Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University
Ralf Kinscherf
Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, Medical Faculty, Philipps University Marburg
Jan Engelmann
Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University
Beat Lutz
Leibniz Institute for Resilience Research
Ari Waisman
Institute for Molecular Medicine and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany.
Iiris Hovatta
Thomas Mittmann
Institute of Physiology, University Medical Center of the Johannes Gutenberg-University
Michael J. Schmeisser
Institute of Anatomy, University Medical Center of the Johannes Gutenberg-University
Marianne B. Müller
Focus Program Translational Neurosciences, University Medical Center of the Johannes Gutenberg-University
Giulia Treccani
Institute of Anatomy, University Medical Center of the Johannes Gutenberg-University