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<p>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 <i>Fgf2</i> 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.</p>

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Environmental enrichment and physical exercise prevent stress-induced social avoidance and blood-brain barrier alterations via Fgf2

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月16日

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  • 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 A. Dudek,
  • Philippe Beauchamp-Kerr,
  • Felix-Antoine Berube,
  • Janick Boissonneault,
  • Francois Borgeat,
  • Lionel Cailhol,
  • Pierre David,
  • Simon Ducharme,
  • Alexandre Dumais,
  • Helen Findlay,
  • Stéphane Guay,
  • Steve Geoffrion,
  • Charles-Edouard Giguere,
  • Roger Godbout,
  • Alexandre Hudon,
  • Robert-Paul Juster,
  • Real Labelle,
  • Marc Lavoie,
  • Myriam Lemyre,
  • Alain Lesage,
  • Cécile Le Page,
  • Olivier Lipp,
  • Sonia Lupien,
  • Jean-Pierre Melun,
  • Marie-France Marin,
  • Carolle Marullo,
  • Francois Noel,
  • Jean-Francois Pelletier,
  • Vincent Tascherau-Dumouchel,
  • Pierrich Plusquellec,
  • Stephane Potvin,
  • Ahmed-Jérome Romain,
  • Marc Sasseville,
  • Daniel St-Laurent,
  • Manuel Serrano,
  • Emmanuel Stip,
  • Christo Todorov,
  • Valerie Tourjman,
  • Samir Taga,
  • Claudia Trudel-Fitzgerald,
  • Martha Francoise Ulysse,
  • Andreas Ziegenhorn,
  • Manon Lebel,
  • Caroline Ménard

摘要

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.