Abstract

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.

The vascular, cellular and molecular changes underlying sex differences in mood disorders are unclear. Here, the authors show that blood-brain barrier dysfunction modulates anxiety- and depressive-like behaviors in female mice and endothelium-specific changes associated with maladaptive responses compared to resilience to stress.

Details

Title
Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue
Author
Dion-Albert, Laurence 1   VIAFID ORCID Logo  ; Cadoret, Alice 1   VIAFID ORCID Logo  ; Doney, Ellen 1   VIAFID ORCID Logo  ; Kaufmann Fernanda Neutzling 1   VIAFID ORCID Logo  ; Dudek, Katarzyna A 1   VIAFID ORCID Logo  ; Daigle Beatrice 1   VIAFID ORCID Logo  ; Parise, Lyonna F 2   VIAFID ORCID Logo  ; Cathomas Flurin 2   VIAFID ORCID Logo  ; Nalia, Samba 3   VIAFID ORCID Logo  ; Hudson, Natalie 4 ; Lebel Manon 1   VIAFID ORCID Logo  ; Aardema Frederic 5 ; Ait Bentaleb Lahcen 5 ; Beauchamp Janique 5 ; Bendahmane Hicham 5 ; Benoit, Elise 5 ; Bergeron Lise 5 ; Bertone Armando 5 ; Bertrand, Natalie 5 ; Felix-Antoine, Berube 5 ; Blanchet, Pierre 5 ; Boissonneault Janick 5 ; Bolduc, Christine J 5 ; Bonin Jean-Pierre 5 ; Borgeat Francois 5 ; Boyer, Richard 5 ; Breault Chantale 5 ; Breton Jean-Jacques 5 ; Briand, Catherine 5 ; Brodeur, Jacques 5 ; Brule Krystele 5 ; Brunet Lyne 5 ; Carriere Sylvie 5 ; Chartrand Carine 5 ; Chenard-Soucy Rosemarie 5 ; Chevrette Tommy 5 ; Cloutier Emmanuelle 5 ; Cloutier, Richard 5 ; Cormier Hugues 5 ; Cote, Gilles 5 ; Cyr, Joanne 5 ; Pierre, David 5 ; De Benedictis Luigi 5 ; Delisle Marie-Claude 5 ; Deschenes, Patricia 5 ; Desjardins, Cindy D 5 ; Desmarais, Gilbert 5 ; Dubreucq Jean-Luc 5 ; Dumont, Mimi 5 ; Dumais Alexandre 5 ; Ethier Guylaine 5 ; Feltrin, Carole 5 ; Felx Amelie 5 ; Findlay, Helen 5 ; Fortier, Linda 5 ; Fortin, Denise 5 ; Fortin, Leo 5 ; Nathe, Francois 5 ; Gagne, Valerie 5 ; Gagnon Marie-Pierre 5 ; Gignac-Hens Marie-Claude 5 ; Charles-Edouard, Giguere 5 ; Godbout, Roger 5 ; Grou, Christine 5 ; Guay Stephane 5 ; Francois, Guillem 5 ; Hachimi-Idrissi Najia 5 ; Herry Christophe 5 ; Hodgins Sheilah 5 ; Saffron, Homayoun 5 ; Jemel Boutheina 5 ; Joyal, Christian 5 ; Kouassi Edouard 5 ; Labelle Real 5 ; Lafortune, Denis 5 ; Lahaie, Michel 5 ; Lahlafi Souad 5 ; Lalonde, Pierre 5 ; Landry, Pierre 5 ; Lapaige Veronique 5 ; Larocque Guylaine 5 ; Larue, Caroline 5 ; Lavoie, Marc 5 ; Leclerc Jean-Jacques 5 ; Lecomte, Tania 5 ; Lecours Cecile 5 ; Leduc, Louise 5 ; Marie-France, Lelan 5 ; Lemieux, Andre 5 ; Lesage, Alain 5 ; Letarte Andree 5 ; Lepage, Jean 5 ; Levesque, Alain 5 ; Lipp, Olivier 5 ; Luck, David 5 ; Lupien, Sonia 5 ; Felix-Antoine, Lusignan 5 ; Lusignan, Richard 5 ; Luyet, Andre J 5 ; Alykhanhthi, Lynhiavu 5 ; Jean-Pierre, Melun 5 ; Morin Celine 5 ; Luc, Nicole 5 ; Noel, Francois 5 ; Normandeau, Louise 5 ; O’Connor Kieron 5 ; Ouellette, Christine 5 ; Parent Veronique 5 ; Parizeau Marie-Helene 5 ; Pelletier Jean-Francois 5 ; Pelletier, Julie 5 ; Pelletier, Marc 5 ; Pierrich, Plusquellec 5 ; Poirier, Diane 5 ; Potvin Stephane 5 ; Prevost Guylaine 5 ; Prevost Marie-Josee 5 ; Racicot, Pierre 5 ; Racine-Gagne Marie-France 5 ; Renaud, Patrice 5 ; Ricard, Nicole 5 ; Rivet Sylvie 5 ; Rolland, Michel 5 ; Sasseville, Marc 5 ; Safadi, Gabriel 5 ; Smith, Sandra 5 ; Smolla, Nicole 5 ; Stip Emmanuel 5 ; Teitelbaum Jakob 5 ; Thibault, Alfred 5 ; Thibault Lucie 5 ; Thibault Stephanye 5 ; Thomas, Frederic 5 ; Todorov Christo 5 ; Tourjman Valerie 5 ; Tranulis Constantin 5 ; Trudeau, Sonia 5 ; Trudel Gilles 5 ; Vacri Nathalie 5 ; Valiquette Luc 5 ; Vanier, Claude 5 ; Villeneuve Kathe 5 ; Villeneuve, Marie 5 ; Vincent, Philippe 5 ; Wolfe, Marcel 5 ; Xiong Lan 5 ; Zizzi, Angela 5 ; Campbell, Matthew 4   VIAFID ORCID Logo  ; Turecki Gustavo 6   VIAFID ORCID Logo  ; Naguib, Mechawar 6   VIAFID ORCID Logo  ; Menard, Caroline 1   VIAFID ORCID Logo 

 Université Laval and CERVO Brain Research, Department of Psychiatry and Neuroscience, Quebec City, Canada (GRID:grid.23856.3a) (ISNI:0000 0004 1936 8390) 
 Icahn School of Medicine at Mount Sinai, Fishberg Department of Neuroscience and the Friedman Brain Institute, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351) 
 Sorbonne Université, Paris, France (GRID:grid.462844.8) (ISNI:0000 0001 2308 1657) 
 Smurfit Institute of Genetics, Trinity College Dublin, Lincoln Place Gate, Dublin 2, Ireland (GRID:grid.8217.c) (ISNI:0000 0004 1936 9705) 
 Centre intégré universitaire de santé et service sociaux Est, Institut universitaire en santé mentale de Montréal, Montreal, Canada (GRID:grid.414210.2) (ISNI:0000 0001 2321 7657) 
 McGill University and Douglas Mental Health University Institute, Department of Psychiatry, Montreal, Canada (GRID:grid.412078.8) (ISNI:0000 0001 2353 5268) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2619578257
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.