Nat. Neurosci. 20, 1752–1760 (2017)

Exposure to chronic emotional stress is linked to the activation of innate immune responses and depression. In Nature Neuroscience, Menard et al. show that stressed mice develop increased permeability of the blood–brain barrier in the nucleus accumbens (NAc) region of the brain, a site associated with mood disorders. Stressed mice exhibit loss of the tight-junction protein claudin-5 and loss of blood–brain barrier integrity in the NAc but not in other brain regions. Loss of claudin-5 expression is also observed in human subjects. Recruitment of circulating CCR2+ monocytes and accumulation of the cytokine IL-6 in the NAc accompany reduced expression of claudin-5, all of which correlates with social avoidance and other measures of depression. These findings reveal how peripheral mediators contribute to depression.