Neuropeptide CRH prevents premature differentiation of OPCs following CNS injury and in early postnatal development
The role of neuropeptides and their receptors in oligodendrocyte (OL) progenitor cells (OPCs) has been largely overlooked so far. Here, we describe a new subpopulation of corticotropin-releasing hormone (CRH)-expressing OPCs. Brain injury rapidly induces transient CRH expression in OPCs that aggregate around injury sites and exhibit an elevated capacity to differentiate into myelinating OLs. As target cells, we identified CRH receptor type 1 (CRHR1)-expressing OPCs, which show a decreased differentiation velocity. CRH/CRHR1 system inactivation increases the speed of OL generation but compromises their long-term survival after acute injury. Under non-injury conditions, CRH/CRHR1 system deficiency leads to increased early postnatal oligodendrogenesis and alterations in adult myelination. Altogether, we show that OPC-derived CRH not only actively influences the injury environment through interaction with CRHR1-expressing OPCs but also identify the G-protein coupled receptor CRHR1 as a critical modulator of oligodendrogenesis during early postnatal development with lasting effects on adult myelination.
Authors
- Dennis Nestvogel (ORCID: https://orcid.org/0000-0002-0568-2552)
- Alessio Attardo (ORCID: https://orcid.org/0000-0003-0665-6011)
- A.F. Ulivi (ORCID: https://orcid.org/0000-0003-4089-9666)
- Leda Dimou (ORCID: https://orcid.org/0000-0002-7818-4407)
- Antonio Rodríguez Infante
- Klaus‐Armin Nave (ORCID: https://orcid.org/0000-0001-8724-9666)
- Torben Ruhwedel (ORCID: https://orcid.org/0000-0002-9535-9395)
- Jan Philipp Delling (ORCID: https://orcid.org/0000-0001-8831-858X)
- Keiichi Itoi (ORCID: https://orcid.org/0000-0002-2860-416X)
- Benoit Boulat
- Michael Czisch (ORCID: https://orcid.org/0000-0002-3682-631X)
- Kenji Sakimura (ORCID: https://orcid.org/0000-0002-8091-8879)
- Jan M. Deussing (ORCID: https://orcid.org/0000-0002-9329-5252)
- Tibor Štark (ORCID: https://orcid.org/0000-0001-8118-9914)
- Simon Chang (ORCID: https://orcid.org/0000-0002-7276-0629)
- Iven-Alex von Mücke-Heim (ORCID: https://orcid.org/0000-0002-5021-9495)
- Clemens Ries (ORCID: https://orcid.org/0009-0003-1364-3240)
- Wiebke Möbius (ORCID: https://orcid.org/0000-0002-2902-7165)
- Julia T von Poblotzki
Institutions
- Universität Ulm (DE)
- Tohoku University (JP)
- Helmholtz Zentrum München (DE)
- Immungenetics (Germany) (DE)
- Max Planck Institute of Psychiatry (DE)
- Institut de Biologie Moléculaire et Cellulaire (FR)
- Max Planck Institute of Immunobiology and Epigenetics (DE)
- Max Planck Institute for Multidisciplinary Sciences (DE)
- Niigata University (JP)
- Leibniz Institute for Neurobiology (DE)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-10-29
- DOI
- https://doi.org/10.1016/j.celrep.2025.116474
- Citations
- 1
- Primary Topic
- Stress Responses and Cortisol
- Type
- article
- Field-Weighted Citation Impact
- 1.11