Environmental enrichment and physical exercise prevent stress-induced social avoidance and blood-brain barrier alterations via Fgf2
Chronic stress promotes blood-brain barrier (BBB) integrity loss leading to passage of inflammatory mediators in mood-regulating brain areas and establishment of depressive behaviors. Conversely, neurovascular adaptations favoring stress resilience and preventive strategies to promote them are undetermined. We report that environmental enrichment dampens stress-induced loss of endothelial tight junction Claudin-5 (Cldn5) along with anxiety- and depression-like behaviors in male mice via an increase in fibroblast growth factor 2 (Fgf2). Coping with voluntary physical exercise also protects the BBB from stress deleterious effects by increasing Fgf2. Fgf2 is mostly expressed by glial cells, and viral-mediated astrocyte-specific Fgf2 upregulation prevents stress-induced social avoidance while downregulation increases stress susceptibility and blunts physical exercise benefits. Treatment of mouse and human endothelial cells with Fgf2 prior an immune challenge reduces BBB dysfunction, Cldn5 loss, and altered signaling supporting its protective role. Circulating FGF2 level is linked with depression severity and symptomatology in men and women reinforcing involvement of this growth factor in mood disorders.
Authors
- Béatrice Daigle (ORCID: https://orcid.org/0000-0002-2953-9515)
- Sonia J. Lupien
- Luisa Bandeira Binder (ORCID: https://orcid.org/0000-0003-2372-8689)
- Alain Lesage (ORCID: https://orcid.org/0000-0002-4226-4683)
- Marie‐France Marin (ORCID: https://orcid.org/0000-0003-0297-5680)
- Alice Cadoret (ORCID: https://orcid.org/0000-0001-8228-3320)
- Charles‐Édouard Giguère (ORCID: https://orcid.org/0000-0002-8507-6412)
- José L. Solano (ORCID: https://orcid.org/0000-0002-1873-4657)
- Émmanuel Stip (ORCID: https://orcid.org/0000-0003-2859-2100)
- Alexandre Dumais (ORCID: https://orcid.org/0000-0002-4480-0064)
- Adeline Collignon (ORCID: https://orcid.org/0009-0005-5086-5648)
- François Coulombe-Rozon
- Katarzyna Dudek (ORCID: https://orcid.org/0000-0003-4894-5268)
- Marc E. Lavoie (ORCID: https://orcid.org/0000-0002-3037-3890)
- Janick Boissonneault
- François Noël (ORCID: https://orcid.org/0000-0001-6813-1347)
- Lionel Cailhol (ORCID: https://orcid.org/0000-0002-5931-8182)
- Alexandre Hudon (ORCID: https://orcid.org/0000-0002-4868-0928)
- Vincent Tascherau-Dumouchel
- Laura Menegatti Bevilacqua (ORCID: https://orcid.org/0000-0001-6460-0249)
- Stéphane Potvin
- Émanuelle Richer
- Andreas Ziegenhorn
- Valérie Tourjman
- François Borgeat
- Christo Todorov
- Marc Sasseville
- Laurence Dion-Albert
- Claudia Trudel-Fitzgerald
- Samir Taga
- Daniel St-Laurent
- Philippe Beauchamp-Kerr
- Olivier Lipp
- Cécile Le Page
- Myriam Lemyre
- Felix-Antoine Berube
- Stéphane Guay
- Helen Findlay
- Steve Geoffrion
- Carolle Marullo
- Manuel Serrano
- Ahmed-Jérome Romain
- Manon Lebel
- Pierre David
- Jean-Francois Pelletier
- Simon Ducharme
- Sam E. J. Paton
- Martha Francoise Ulysse
- Real Labelle
- Caroline Ménard
Institutions
- Institut Universitaire en Santé Mentale de Québec (CA)
- Centres Intégré Universitaires de Santé et de Services Sociaux (CA)
- Université Laval (CA)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-01-16
- DOI
- https://doi.org/10.1038/s41467-025-68058-9
- Citations
- 1
- Primary Topic
- Barrier Structure and Function Studies
- Type
- article
- Field-Weighted Citation Impact
- 30.63