Electronic Poster | Session 1

042 – Molecular adaptations of the blood-brain barrier promoting depression or stress resilience

Katarzyna Anna Dudek (1*) – Manon Lebel (1) – Laurence Dion-Albert (1) – Katherine LeClair (2) – Ellen Tuck (1, 3) – Carmen Ferrer Perez (4) – Sam A Golden (5) – Naguib Mechawar (6) – Scott J Russo (2) – Caroline Menard (1)
Université Laval & CERVO Brain Research Center, Quebec City (Canada) (1) – Icahn School of Medicine at Mount Sinai & Friedman Brain Institute, New York (USA) (2) – Trinity College Dublin, Dublin (Ireland) (3) – University of Valencia, Valencia (Spain) (4) – University of Washington, Seattle (USA) (5) – McGill University & Douglas Mental Health University Institute, Montreal (Canada) (6)

Abstract: Major depressive disorder (MDD) is the leading cause of disability worldwide and will affect20% of individuals. MDD is a recurrent condition and only 30% of patients remit completely. This low efficacy level suggests that conventional treatments do not address causal biological factors. Clinical studies report higher prevalence of MDD in patients suffering from vascular diseases, indicating that increased inflammation and vascular dysfunction may contribute to depression pathogenesis. We showed that chronic stress, depression’s main environmental risk factor, induces blood-brain barrier (BBB) leakage in the nucleus accumbens (NAc) of mice, promoting depression-like behaviors. Here, we characterized molecular adaptations underlying stress susceptibility (SS) vs resilience (RES) in the NAc endothelial cells of C57Bl6 mice. Mice were subjected to 10-day chronic social defeat stress followed by social interaction test 24h later to determine behavioral phenotype. Then, NAc punches were collected and cell-specific magnetic activated cell sorting was performed followed by transcriptome-wide gene-level expression analyses. We observed specific gene expression patterns in endothelial cells of the NAc of SS vs RES. Importantly, such changes were also present in RES vs control mice indicating that BBB molecular adaptations are necessary to maintain its integrity under chronic stress conditions. We confirmed changes in BBB-related gene expression in postmortem NAc samples of MDD patients supporting a role for the vasculature in depression and possibly novel therapeutic strategies.
Funding: Brain & Behavior Research Foundation (NARSAD), Canada First Research Excellence Fund (Sentinel North Initiative), Fonds Recherche du Québec – Santé, CERVO Brain Research Center, Fonds Hélène-Hallé & Faculty of Medicine (Université Laval)