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

Dion-Albert, L., Cadoret, A., Doney, E., Kaufmann, F. N., Dudek, K. A., Daigle, B., Parise, L. F., Cathomas, F., Samba, N., Hudson, N., Lebel, M., Aardema, F., Ait Bentaleb, L., Beauchamp, J., Bendahmane, H., Benoit, E., Bergeron, L., Bertone, A., Bertrand, N., Berube, F.-A., Blanchet, P., Boissonneault, J., Bolduc, C. J., Bonin, J.-P., Borgeat, F., Boyer, R., Breault, C., Breton, J.-J., Briand, C., Brodeur, J., Brule, K., Brunet, L., Carriere, S., Chartrand, C., Chenard-Soucy, R., Chevrette, T., Cloutier, E., Cloutier, R., Cormier, H., Cote, G., Cyr, J., David, P., De Benedictis, L., Delisle, M.-C., Deschenes, P., Desjardins, C. D., Desmarais, G., Dubreucq, J.-L., Dumont, M., Dumais, A., Ethier, G., Feltrin, C., Felx, A., Findlay, H., Fortier, L., Fortin, D., Fortin, L., Francois, N., Gagne, V., Gagnon, M.-P., Gignac-Hens, M.-C., Giguere, C.-E., Godbout, R., Grou, C., Guay, S., Guillem, F., Hachimi-Idrissi, N., Herry, C., Hodgins, S., Homayoun, S., Jemel, B., Joyal, C. C., Kouassi, E., Labelle, R., Lafortune, D., Lahaie, M., Lahlafi, S., Lalonde, P., Landry, P., Lapaige, V., Larocque, G., Larue, C., Lavoie, M., Leclerc, J.-J., Lecomte, T., Lecours, C., Leduc, L., Lelan, M.-F., Lemieux, A., Lesage, A., Letarte, A., Lepage, J., Levesque, A., Lipp, O., Luck, D., Lupien, S., Lusignan, F.-A., Lusignan, R., Luyet, A. J., Lynhiavu, A., Melun, J.-P., Morin, C., Nicole, L., Noel, F., Normandeau, L., O’Connor, K., Ouellette, C., Parent, V., Parizeau, M.-H., Pelletier, J.-F., Pelletier, J., Pelletier, M., Plusquellec, P., Poirier, D., Potvin, S., Prevost, G., Prevost, M.-J., Racicot, P., Racine-Gagne, M.-F., Renaud, P., Ricard, N., Rivet, S., Rolland, M., Sasseville, M., Safadi, G., Smith, S., Smolla, N., Stip, E., Teitelbaum, J., Thibault, A., Thibault, L., Thibault, S., Thomas, F., Todorov, C., Tourjman, V., Tranulis, C., Trudeau, S., Trudel, G., Vacri, N., Valiquette, L., Vanier, C., Villeneuve, K., Villeneuve, M., Vincent, P., Wolfe, M., Xiong, L., Zizzi, A., Campbell, M., Turecki, G., Mechawar, N. et Menard, C. (2022). Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue. Nature Communications, 13 (1). p. 164. ISSN 2041-1723 DOI 10.1038/s41467-021-27604-x

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Résumé

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.

Type de document:	Article
Mots-clés libres:	Blood–brain barrier Depression Diagnostic markers Stress and resilience
Date de dépôt:	14 août 2023 13:31
Dernière modification:	14 août 2023 13:31
Version du document déposé:	Version officielle de l'éditeur
URI:	https://depot-e.uqtr.ca/id/eprint/10834

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