Mechanisms of stress-induced neurovascular damage promoting immune infiltration and depression-like behaviors

Major depressive disorder is associated with heightened peripheral inflammation that is casually linked to depression symptoms. Despite years of intensive research and ongoing clinical trials to test antidepressant efficacy of immune modulatory drugs that target systemic inflammation, it is still unclear how the peripheral immune system interfaces with mood-related brain circuitry to control depression-like behavioral responses. In this proposal we show that chronic stress induces neurovascular damage that weakens the blood brain barrier to allow immune infiltration and expression of depression-like behaviors.