Social stress induces neurovascular pathology promoting depression

By C. Ménard, M. Pfau, G. Hodes, V. Kana, Victoria Wang, Sylvain Bouchard, Aki Takahashi, M. Flanigan, Hossein Aleyasin, Katherine B Leclair and 13 more. Nature Neuroscience, 2017

899 citations recorded by the source corpus.

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. Chronic social defeat stress induces loss of protein claudin-5, leading to abnormalities in blood vessel morphology, increased blood brain barrier permeability, infiltration of immune signals and depression-like behaviors.

Subfields: Behavioral Neuroscience, Biological Psychiatry, Neurology

View Paper: https://www.semanticscholar.org/paper/66079f02fd3a498f89804c77717db403860e60a8

How researchers see this paper

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In Behavioral Neuroscience

1. C. Nemeroff
2. Eléonore Beurel
3. M. Toups

In Biological Psychiatry

1. C. Nemeroff
2. Eléonore Beurel
3. M. Toups

In Neurology

1. C. Nemeroff
2. Eléonore Beurel
3. M. Toups

Citations in the corpus

• Neuroinflammation and depression: A review (2020, background): “Chronic stress also reduces expression of claudin-5 in the nucleus accumbens, which alters BBB permeability and facilitates entry of IL-6 into the brain (Menard et al., 2017).”
• The Bidirectional Relationship of Depression and Inflammation: Double Trouble (2020, background): “The field of neuroinflammation has been focusing on central cytokines, whereas peripheral cytokines certainly contribute to behavioral effects, as suggested by findings showing that blocking peripheral cytokines is sufficient to tighten the BBB and that blocking BBB disruption is sufficient to exhib”