Major depessive disorder (MDD) is linked to increased levels of circulating pro-inflammatory cytokines, such as interleukin 6 (IL-6). Among mice subjected to chronic social defeat stress (a rodent model of depression), the expression of the tight junction protein claudin-5 (CLDN5) at the blood–brain barrier (BBB) was reduced in the nucleus accumbens (NAc) in animals with greater susceptibility to depression-like behaviour; people with MDD also showed reduced CLDN5 mRNA levels in the NAc. Knock-down of CLDN5 in mice increased BBB permeability and brain IL-6 levels, and induced depression-like behaviours, suggesting a role for CLDN5 in MDD.
References
Menard, C. et al. Social stress induces neurovascular pathology promoting depression. Nat. Neurosci. 20, 1752–1760 (2017)
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Lewis, S. Stressful depression. Nat Rev Neurosci 19, 3 (2018). https://doi.org/10.1038/nrn.2017.153
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DOI: https://doi.org/10.1038/nrn.2017.153