TY - JOUR
T1 - Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue
AU - Signature Consortium
AU - Dion-Albert, Laurence
AU - Cadoret, Alice
AU - Doney, Ellen
AU - Kaufmann, Fernanda Neutzling
AU - Dudek, Katarzyna A.
AU - Daigle, Beatrice
AU - Parise, Lyonna F.
AU - Cathomas, Flurin
AU - Samba, Nalia
AU - Hudson, Natalie
AU - Lebel, Manon
AU - Aardema, Frederic
AU - Ait Bentaleb, Lahcen
AU - Beauchamp, Janique
AU - Bendahmane, Hicham
AU - Benoit, Elise
AU - Bergeron, Lise
AU - Bertone, Armando
AU - Bertrand, Natalie
AU - Berube, Felix Antoine
AU - Blanchet, Pierre
AU - Boissonneault, Janick
AU - Bolduc, Christine J.
AU - Bonin, Jean Pierre
AU - Borgeat, Francois
AU - Boyer, Richard
AU - Breault, Chantale
AU - Breton, Jean Jacques
AU - Briand, Catherine
AU - Brodeur, Jacques
AU - Brule, Krystele
AU - Brunet, Lyne
AU - Carriere, Sylvie
AU - Chartrand, Carine
AU - Chenard-Soucy, Rosemarie
AU - Chevrette, Tommy
AU - Cloutier, Emmanuelle
AU - Cloutier, Richard
AU - Cormier, Hugues
AU - Cote, Gilles
AU - Cyr, Joanne
AU - David, Pierre
AU - De Benedictis, Luigi
AU - Delisle, Marie Claude
AU - Deschenes, Patricia
AU - Desjardins, Cindy D.
AU - Desmarais, Gilbert
AU - Dubreucq, Jean Luc
AU - Dumont, Mimi
AU - Stip, Emmanuel
N1 - Funding Information:
The authors thank Valerie Catudal and Melissa Murillo Radtke from Genome Quebec, Isabelle Labonté from the CERVO FACS core, Julie-Christine Lévesque from the CRCHU de Quebec Bioimaging Platform of Infectious Disease Research Center as well as the CERVO Brain Research Centre housing facility staff (special thanks to Louisabelle Gagnon) for their work and support. This research was supported by the Canadian Institutes for Health Research (CIHR, Project Grant #427011 to C.M.), Fonds de recherche du Quebec–Sante (FRQS, Junior 1 Salary Award to C.M.) and C.M. Sentinel North Research Chair funded by Canada First Research Excellence Fund. L.F.P. and F.C. are supported by a National Institute of Health grant R01MH104559. M.C. is supported by grants from the European Research Council (ERC: Retina-Rhythm), The Irish Research Council (IRC), and an SFI Centres grant supported in part by a research grant from SFI under grant number 16/RC/3948 and co-funded under the European Regional Development fund by FutureNeuro industry partners. L.DA., F.N.K., K.A.D. and F.C. are supported by scholarships or fellowships from CIHR, Sentinel North, FRQS, and the Swiss National Science Foundation, respectively. The Douglas-Bell Canada Brain Bank is funded by the RQSHA (FRQS) and a platform support grant from Healthy Brain Healthy Lives (Canada First Research Excellence Fund).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-021-27604-x
DO - 10.1038/s41467-021-27604-x
M3 - Article
C2 - 35013188
AN - SCOPUS:85122874135
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 164
ER -