Molecular adaptations of the blood-brain barrier promoting depression or stress resilience Major depressive disorder (MDD) will affect 1 out of 5 individ- uals throughout their lifetime and is now considered the leading cause of disabilities worldwide. Depression is a recurrent con- dition and only 30% of patients completely remit. This lack of efficacy suggests that neuron-centric traditional treatments do not address important causal biological factors. Clinical studies report higher prevalence of MDD in patients suffering from cardiovascu- lar diseases or stroke, indicating that increased inflammation and vascular dysfunction could contribute to depression pathogenesis. We recently showed that chronic social stress induces blood-brain barrier (BBB) leakiness in the nucleus accumbens (NAc) of mice, promoting depression-like behaviors. The BBB is an active inter- face preventing deleterious circulating signals to penetrate the healthy brain. Chronic stress is depression’s main environmental risk factor and the NAc is a forebrain nucleus playing a crucial role in stress responses. Interestingly, not all stressed mice displayed depression-like behaviors and loss of BBB integrity suggesting that neurovascular adaptations may help maintain BBB integrity leading to stress resilience.
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