Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue
Authors: Dion-Albert Laurence , Cadoret Alice , Doney Ellen , Kaufmann Fernanda Neutzling , Dudek Katarzyna A. , Daigle Beatrice , Parise Lyonna F. , Cathomas Flurin , Samba Nalia , Hudson Natalie , Lebel Manon ,   Signature Consortium, Aardema Frederic , Ait Bentaleb Lahcen , Beauchamp Janique , Bendahmane Hicham , Benoit Elise , Bergeron Lise , Bertone Armando , Bertrand Natalie , Berube Felix-Antoine , Blanchet Pierre , Boissonneault Janick , Bolduc Christine J. , Bonin Jean-Pierre , Borgeat Francois , Boyer Richard , Breault Chantale , Breton Jean-Jacques , Briand Catherine , Brodeur Jacques , Brule Krystele , Brunet Lyne , Carriere Sylvie , Chartrand Carine , Chenard-Soucy Rosemarie , Chevrette Tommy , Cloutier Emmanuelle , Cloutier Richard , Cormier Hugues , Cote Gilles , Cyr Joanne , David Pierre , De Benedictis Luigi , Delisle Marie-Claude , Deschenes Patricia , Desjardins Cindy D. , Desmarais Gilbert , Dubreucq Jean-Luc , Dumont Mimi , Dumais Alexandre , Ethier Guylaine , Feltrin Carole , Felx Amelie , Findlay Helen , Fortier Linda , Fortin Denise , Fortin Leo , Francois Nathe , Gagne Valerie , Gagnon Marie-Pierre , Gignac-Hens Marie-Claude , Giguere Charles-Edouard , Godbout Roger , Grou Christine , Guay Stephane , Guillem Francois , Hachimi-Idrissi Najia , Herry Christophe , Hodgins Sheilah , Homayoun Saffron , Jemel Boutheina , Joyal Christian , Kouassi Edouard , Labelle Real , Lafortune Denis , Lahaie Michel , Lahlafi Souad , Lalonde Pierre , Landry Pierre , Lapaige Veronique , Larocque Guylaine , Larue Caroline , Lavoie Marc , Leclerc Jean-Jacques , Lecomte Tania , Lecours Cecile , Leduc Louise , Lelan Marie-France , Lemieux Andre , Lesage Alain , Letarte Andree , Lepage Jean , Levesque Alain , Lipp Olivier , Luck David , Lupien Sonia , Lusignan Felix-Antoine , Lusignan Richard , Luyet Andre J. , Lynhiavu Alykhanhthi , Melun Jean-Pierre , Morin Celine , Nicole Luc , Noel Francois , Normandeau Louise , O’Connor Kieron , Ouellette Christine , Parent Veronique , Parizeau Marie-Helene , Pelletier Jean-Francois , Pelletier Julie , Pelletier Marc , Plusquellec Pierrich , Poirier Diane , Potvin Stephane , Prevost Guylaine , Prevost Marie-Josee , Racicot Pierre , Racine-Gagne Marie-France , Renaud Patrice , Ricard Nicole , Rivet Sylvie , Rolland Michel , Sasseville Marc , Safadi Gabriel , Smith Sandra , Smolla Nicole , Stip Emmanuel , Teitelbaum Jakob , Thibault Alfred , Thibault Lucie , Thibault Stephanye , Thomas Frederic , Todorov Christo , Tourjman Valerie , Tranulis Constantin , Trudeau Sonia , Trudel Gilles , Vacri Nathalie , Valiquette Luc , Vanier Claude , Villeneuve Kathe , Villeneuve Marie , Vincent Philippe , Wolfe Marcel , Xiong Lan , Zizzi Angela , Campbell Matthew , Turecki Gustavo , Mechawar Naguib , Menard Caroline 
Published: January 2022

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.