| First Author | Menard C | Year | 2017 |
| Journal | Nat Neurosci | Volume | 20 |
| Issue | 12 | Pages | 1752-1760 |
| PubMed ID | 29184215 | Mgi Jnum | J:258031 |
| Mgi Id | MGI:6116632 | Doi | 10.1038/s41593-017-0010-3 |
| Citation | Menard C, et al. (2017) Social stress induces neurovascular pathology promoting depression. Nat Neurosci 20(12):1752-1760 |
| abstractText | 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. |
