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Sunderland Repository records the research produced by the University of Sunderland including practice-based research and theses.

Social stress induces neurovascular pathology promoting depression

Menard, Caroline, Pfau, Madeline L., Hodes, Georgia E., Kana, Veronika, Wang, Victoria X., Bouchard, Sylvain, Takahashi, Aki, Flanigan, Meghan E., Aleyasin, Hossein, LeClair, Katherine B., Janssen, William G., Labonté, Benoit, Parise, Eric M., Lorsch, Zachary S., Golden, Sam A., Heshmati, Mitra, Tamminga, Carol, Turecki, Gustavo, Campbell, Matthew, Fayad, Zahi A., Tang, Cheuk Ying, Merad, Miriam and Russo, Scott J. (2017) Social stress induces neurovascular pathology promoting depression. Nature Neuroscience, 20 (12). pp. 1752-1760. ISSN 1097-6256

Item Type: Article


Studies suggest that heightened peripheral inflammation contributes to the pathogenesis of major depressive disorder. We investigated the effect of chronic social defeat stress, a mouse model of depression, on blood–brain barrier (BBB) permeability and infiltration of peripheral immune signals. We found reduced expression of the endothelial cell tight junction protein claudin-5 (Cldn5) and abnormal blood vessel morphology in nucleus accumbens (NAc) of stress-susceptible but not resilient mice. CLDN5 expression was also decreased in NAc of depressed patients. Cldn5 downregulation was sufficient to induce depression-like behaviors following subthreshold social stress whereas chronic antidepressant treatment rescued Cldn5 loss and promoted resilience. Reduced BBB integrity in NAc of stress-susceptible or mice injected with adeno-associated virus expressing shRNA against Cldn5 caused infiltration of the peripheral cytokine interleukin-6 (IL-6) into brain parenchyma and subsequent expression of depression-like behaviors. These findings suggest that chronic social stress alters BBB integrity through loss of tight junction protein Cldn5, promoting peripheral IL-6 passage across the BBB and depression

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Depositing User: Matthew Campbell


Item ID: 13132
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ISSN: 1097-6256
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ORCID for Matthew Campbell: ORCID iD

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Date Deposited: 24 Feb 2021 11:01
Last Modified: 24 Feb 2021 11:01


Author: Matthew Campbell ORCID iD
Author: Caroline Menard
Author: Madeline L. Pfau
Author: Georgia E. Hodes
Author: Veronika Kana
Author: Victoria X. Wang
Author: Sylvain Bouchard
Author: Aki Takahashi
Author: Meghan E. Flanigan
Author: Hossein Aleyasin
Author: Katherine B. LeClair
Author: William G. Janssen
Author: Benoit Labonté
Author: Eric M. Parise
Author: Zachary S. Lorsch
Author: Sam A. Golden
Author: Mitra Heshmati
Author: Carol Tamminga
Author: Gustavo Turecki
Author: Zahi A. Fayad
Author: Cheuk Ying Tang
Author: Miriam Merad
Author: Scott J. Russo

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Faculty of Health Sciences and Wellbeing

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