Sam E.J. Paton, José L. Solano, Alice Cadoret, Adeline Collignon, Luisa Bandeira Binder, Béatrice Daigle, Laura Menegatti Bevilacqua, Émanuelle Richer, François Coulombe-Rozon, Laurence Dion-Albert, Katarzyna Dudek, Philippe Beauchamp-Kerr, Felix-Antoine Berube, Janick Boissonneault, François Borgeat, Lionel Cailhol, Pierre David, Simon Ducharme, Alexandre Dumais, Helen Findlay, Stéphane Guay, Steve Geoffrion, Charles‐Édouard Giguère, Roger Godbout, Alexandre Hudon, Robert-Paul Juster, Real Labelle, Marc E. Lavoie, Myriam Lemyre, Alain Lesage, Cécile Le Page, Olivier Lipp, Sonia J. Lupien, Jean-Pierre Melun, Marie‐France Marin, Carolle Marullo, François Noël, Jean-Francois Pelletier, Vincent Tascherau-Dumouchel, Pierrich Plusquellec, Stéphane Potvin, Ahmed-Jérome Romain, Marc Sasseville, Daniel St-Laurent, Manuel Serrano, Émmanuel Stip, Christo Todorov, Valérie Tourjman, Samir Taga, Claudia Trudel-Fitzgerald, Martha Francoise Ulysse, Andreas Ziegenhorn, Manon Lebel, Caroline Ménard
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.