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

Hudson, Natalie; Campbell, Matthew

doi:http://dx.doi.org/10.1038/s41467-021-27604-x

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

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Primary s41467-021-27604-x.pdf (7.89 MB)

Date

2022

Authors

Hudson, Natalie

Campbell, Matthew

Citation

Dion-Albert, L. and Cadoret, A. and Doney, E. and Kaufmann, F.N. and Dudek, K.A. and Daigle, B. and Parise, L.F. and Cathomas, F. and Samba, N. and Hudson, N. and Lebel, M. and Aardema, F. and Ait Bentaleb, L. and Beauchamp, J. and Bendahmane, H. and Benoit, E. and Bergeron, L. and Bertone, A. and Bertrand, N. and Berube, F.-A. and Blanchet, P. and Boissonneault, J. and Bolduc, C.J. and Bonin, J.-P. and Borgeat, F. and Boyer, R. and Breault, C. and Breton, J.-J. and Briand, C. and Brodeur, J. and Brule, K. and Brunet, L. and Carriere, S. and Chartrand, C. and Chenard-Soucy, R. and Chevrette, T. and Cloutier, E. and Cloutier, R. and Cormier, H. and Cote, G. and Cyr, J. and David, P. and De Benedictis, L. and Delisle, M.-C. and Deschenes, P. and Desjardins, C.D. and Desmarais, G. and Dubreucq, J.-L. and Dumont, M. and Dumais, A. and Ethier, G. and Feltrin, C. and Felx, A. and Findlay, H. and Fortier, L. and Fortin, D. and Fortin, L. and Francois, N. and Gagne, V. and Gagnon, M.-P. and Gignac-Hens, M.-C. and Giguere, C.-E. and Godbout, R. and Grou, C. and Guay, S. and Guillem, F. and Hachimi-Idrissi, N. and Herry, C. and Hodgins, S. and Homayoun, S. and Jemel, B. and Joyal, C. and Kouassi, E. and Labelle, R. and Lafortune, D. and Lahaie, M. and Lahlafi, S. and Lalonde, P. and Landry, P. and Lapaige, V. and Larocque, G. and Larue, C. and Lavoie, M. and Leclerc, J.-J. and Lecomte, T. and Lecours, C. and Leduc, L. and Lelan, M.-F. and Lemieux, A. and Lesage, A. and Letarte, A. and Lepage, J. and Levesque, A. and Lipp, O. and Luck, D. and Lupien, S. and Lusignan, F.-A. and Lusignan, R. and Luyet, A.J. and Lynhiavu, A. and Melun, J.-P. and Morin, C. and Nicole, L. and Noel, F. and Normandeau, L. and O’Connor, K. and Ouellette, C. and Parent, V. and Parizeau, M.-H. and Pelletier, J.-F. and Pelletier, J. and Pelletier, M. and Plusquellec, P. and Poirier, D. and Potvin, S. and Prevost, G. and Prevost, M.-J. and Racicot, P. and Racine-Gagne, M.-F. and Renaud, P. and Ricard, N. and Rivet, S. and Rolland, M. and Sasseville, M. and Safadi, G. and Smith, S. and Smolla, N. and Stip, E. and Teitelbaum, J. and Thibault, A. and Thibault, L. and Thibault, S. and Thomas, F. and Todorov, C. and Tourjman, V. and Tranulis, C. and Trudeau, S. and Trudel, G. and Vacri, N. and Valiquette, L. and Vanier, C. and Villeneuve, K. and Villeneuve, M. and Vincent, P. and Wolfe, M. and Xiong, L. and Zizzi, A. and Campbell, M. and Turecki, G. and Mechawar, N. and Menard, C., Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue, Nature Communications, 13, 1, 2022

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.