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Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue

2022; Nature Portfolio; Volume: 13; Issue: 1 Linguagem: Inglês

10.1038/s41467-021-27604-x

2041-1723

Laurence Dion‐Albert, Alice Cadoret, Ellen Doney, Fernanda Neutzling Kaufmann, Katarzyna Dudek, Béatrice Daigle, Lyonna F. Parise, Flurin Cathomas, Nalia Samba, Natalie Hudson, Manon Lebel, Frederic Aardema, Lahcen Aït Bentaleb, Janique Beauchamp, Hicham Bendahmane, Élise Benoît, Lise Bergeron, Armando Bertone, Natalie Bertrand, Félix-Antoine Bérubé, Pierre J. Blanchet, Janick Boissonneault, Christine J. Bolduc, Jean‐Pierre Bonin, François Borgeat, Richard Boyer, Chantale Breault, Jean‐Jacques Breton, Catherine Briand, Jacques Brodeur, Krystele Brule, Lyne Brunet, Sylvie Carrière, Carine Chartrand, Rosemarie Chenard-Soucy, Tommy Chevrette, Emmanuelle Cloutier, Richard Cloutier, Hugues J. Cormier, Gilles Côté, Joanne Cyr, Pierre David, Luigi De Benedictis, Marie-Claude Delisle, Patricia Deschenes, Cindy D. Desjardins, Gilbert Desmarais, Jean-Luc Dubreucq, Mimi Dumont, Alexandre Dumais, Guylaine Ethier, Carole Feltrin, Amelie Felx, Helen Findlay, Linda Fortier, Denise Fortin, Leo Fortin, Nathe François, Valérie Gagné, Marie-Pierre Gagnon, Marie-Claude Gignac-Hens, Charles–Édouard Giguère, Roger Godbout, Christine Grou, Stéphane Guay, François Guillem, Najia Hachimi-Idrissi, Christophe L. Herry, Sheilah Hodgins, Saffron Homayoun, Boutheina Jemel, Christian C. Joyal, Édouard Kouassi, Réal Labelle, Denis Lafortune, Michel Lahaie, Souad Lahlafi, Pierre Lalonde, Pierre Landry, V. Lapaige, Guylaine Larocque, C Larue, Marc E. Lavoie, Jean-Jacques Leclerc, Tania Lecomte, Cecile Lecours, Louise E. LeDuc, Marie-France Lelan, André Lemieux, Alain Lesage, Andree Letarte, J. Y. Lepage, Alain Lévesque, Olivier Lipp, David Luck, Sonia Lupien, Felix-Antoine Lusignan, Richard Lusignan, Andre J. Luyet, Alykhanhthi Lynhiavu, Jean-Pierre Melun, Celine Morin, Luc Nicole, F. Noël, Louise Normandeau, Kieron O’Connor, Christine Ouellette, Veronique Parent, Marie‐Hélène Parizeau, Jean‐François Pelletier, Julie Pelletier, Marc Pelletier, Pierrich Plusquellec, Diane Poirier, Stéphane Potvin, Guylaine Prevost, Marie-Josee Prevost, Pierre Racicot, Marie-France Racine-Gagne, Patrice Renaud, Nicole Ricard, Sylvie Rivet, Michel Rolland, Marc Sasseville, Gabriel Safadi, Sandra L. Smith, Nicole Smolla, Émmanuel Stip, Jakob Teitelbaum, Alfred Thibault, Lucie Thibault, Stephanye Thibault, Frédéric Thomas, Christo Todorov, Valérie Tourjman, Constantin Tranulis, Sonia Trudeau, Gilles Trudel, Nathalie Vacri, Luc Valiquette, Claude Vanier, Kathe Villeneuve, Marie Villeneuve, Philippe Vincent, M.M. Wolfe, Lan Xiong, Angela Zizzi, Matthew Campbell, Gustavo Turecki, Naguib Mechawar, Caroline Ménard,

Anesthesia and Neurotoxicity Research

Prevalence, symptoms, and treatment of depression suggest that major depressive disorders (MDD) present sex differences. Social stress-induced neurovascular pathology is associated with depressive symptoms in male mice; however, this association is unclear in females. Here, we report that chronic social and subchronic variable stress promotes blood-brain barrier (BBB) alterations in mood-related brain regions of female mice. Targeted disruption of the BBB in the female prefrontal cortex (PFC) induces anxiety- and depression-like behaviours. By comparing the endothelium cell-specific transcriptomic profiling of the mouse male and female PFC, we identify several pathways and genes involved in maladaptive stress responses and resilience to stress. Furthermore, we confirm that the BBB in the PFC of stressed female mice is leaky. Then, we identify circulating vascular biomarkers of chronic stress, such as soluble E-selectin. Similar changes in circulating soluble E-selectin, BBB gene expression and morphology can be found in blood serum and postmortem brain samples from women diagnosed with MDD. Altogether, we propose that BBB dysfunction plays an important role in modulating stress responses in female mice and possibly MDD.