Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue.
Animals
Anxiety
/ genetics
Biological Transport
Biomarkers
/ metabolism
Blood-Brain Barrier
/ metabolism
Depression
/ genetics
Depressive Disorder, Major
/ genetics
E-Selectin
/ genetics
Endothelial Cells
/ metabolism
Female
Gene Expression Profiling
Humans
Male
Mice
Nerve Tissue Proteins
/ genetics
Nucleus Accumbens
/ blood supply
Prefrontal Cortex
/ blood supply
Sex Characteristics
Stress, Psychological
/ genetics
Transcriptome
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 01 2022
10 01 2022
Historique:
received:
28
04
2021
accepted:
09
11
2021
entrez:
11
1
2022
pubmed:
12
1
2022
medline:
11
2
2022
Statut:
epublish
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.
Identifiants
pubmed: 35013188
doi: 10.1038/s41467-021-27604-x
pii: 10.1038/s41467-021-27604-x
pmc: PMC8748803
doi:
Substances chimiques
Biomarkers
0
E-Selectin
0
Nerve Tissue Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
164Subventions
Organisme : NIMH NIH HHS
ID : R01 MH104559
Pays : United States
Organisme : CIHR
ID : 427011
Pays : Canada
Investigateurs
Frederic Aardema
(F)
Lahcen Ait Bentaleb
(L)
Janique Beauchamp
(J)
Hicham Bendahmane
(H)
Elise Benoit
(E)
Lise Bergeron
(L)
Armando Bertone
(A)
Natalie Bertrand
(N)
Felix-Antoine Berube
(FA)
Pierre Blanchet
(P)
Janick Boissonneault
(J)
Christine J Bolduc
(CJ)
Jean-Pierre Bonin
(JP)
Francois Borgeat
(F)
Richard Boyer
(R)
Chantale Breault
(C)
Jean-Jacques Breton
(JJ)
Catherine Briand
(C)
Jacques Brodeur
(J)
Krystele Brule
(K)
Lyne Brunet
(L)
Sylvie Carriere
(S)
Carine Chartrand
(C)
Rosemarie Chenard-Soucy
(R)
Tommy Chevrette
(T)
Emmanuelle Cloutier
(E)
Richard Cloutier
(R)
Hugues Cormier
(H)
Gilles Cote
(G)
Joanne Cyr
(J)
Pierre David
(P)
Luigi De Benedictis
(L)
Marie-Claude Delisle
(MC)
Patricia Deschenes
(P)
Cindy D Desjardins
(CD)
Gilbert Desmarais
(G)
Jean-Luc Dubreucq
(JL)
Mimi Dumont
(M)
Alexandre Dumais
(A)
Guylaine Ethier
(G)
Carole Feltrin
(C)
Amelie Felx
(A)
Helen Findlay
(H)
Linda Fortier
(L)
Denise Fortin
(D)
Leo Fortin
(L)
Nathe Francois
(N)
Valerie Gagne
(V)
Marie-Pierre Gagnon
(MP)
Marie-Claude Gignac-Hens
(MC)
Charles-Edouard Giguere
(CE)
Roger Godbout
(R)
Christine Grou
(C)
Stephane Guay
(S)
Francois Guillem
(F)
Najia Hachimi-Idrissi
(N)
Christophe Herry
(C)
Sheilah Hodgins
(S)
Saffron Homayoun
(S)
Boutheina Jemel
(B)
Christian Joyal
(C)
Edouard Kouassi
(E)
Real Labelle
(R)
Denis Lafortune
(D)
Michel Lahaie
(M)
Souad Lahlafi
(S)
Pierre Lalonde
(P)
Pierre Landry
(P)
Veronique Lapaige
(V)
Guylaine Larocque
(G)
Caroline Larue
(C)
Marc Lavoie
(M)
Jean-Jacques Leclerc
(JJ)
Tania Lecomte
(T)
Cecile Lecours
(C)
Louise Leduc
(L)
Marie-France Lelan
(MF)
Andre Lemieux
(A)
Alain Lesage
(A)
Andree Letarte
(A)
Jean Lepage
(J)
Alain Levesque
(A)
Olivier Lipp
(O)
David Luck
(D)
Sonia Lupien
(S)
Felix-Antoine Lusignan
(FA)
Richard Lusignan
(R)
Andre J Luyet
(AJ)
Alykhanhthi Lynhiavu
(A)
Jean-Pierre Melun
(JP)
Celine Morin
(C)
Luc Nicole
(L)
Francois Noel
(F)
Louise Normandeau
(L)
Kieron O'Connor
(K)
Christine Ouellette
(C)
Veronique Parent
(V)
Marie-Helene Parizeau
(MH)
Jean-Francois Pelletier
(JF)
Julie Pelletier
(J)
Marc Pelletier
(M)
Pierrich Plusquellec
(P)
Diane Poirier
(D)
Stephane Potvin
(S)
Guylaine Prevost
(G)
Marie-Josee Prevost
(MJ)
Pierre Racicot
(P)
Marie-France Racine-Gagne
(MF)
Patrice Renaud
(P)
Nicole Ricard
(N)
Sylvie Rivet
(S)
Michel Rolland
(M)
Marc Sasseville
(M)
Gabriel Safadi
(G)
Sandra Smith
(S)
Nicole Smolla
(N)
Emmanuel Stip
(E)
Jakob Teitelbaum
(J)
Alfred Thibault
(A)
Lucie Thibault
(L)
Stephanye Thibault
(S)
Frederic Thomas
(F)
Christo Todorov
(C)
Valerie Tourjman
(V)
Constantin Tranulis
(C)
Sonia Trudeau
(S)
Gilles Trudel
(G)
Nathalie Vacri
(N)
Luc Valiquette
(L)
Claude Vanier
(C)
Kathe Villeneuve
(K)
Marie Villeneuve
(M)
Philippe Vincent
(P)
Marcel Wolfe
(M)
Lan Xiong
(L)
Angela Zizzi
(A)
Informations de copyright
© 2022. The Author(s).
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