Printed Poster | Session 2

007 – Role of blood-brain barrier transport in stress-induced immune response and depression

Fernanda Neutzling Kaufmann (1) – Katarzyna Dudek (1) – Laurence Albert-Dion (1) – Manon Lebel (1) – Caroline Menard (1)
Laval University, Department of Psychiatry and Neuroscience, Faculty of Medicine and CERVO Brain Research Center, Quebec City, Canada (1)

Major depressive disorder (MDD) will affect 7% of population yearly and 20% throughout lifetime. MDD is a heterogeneous and multifactorial disorder involving many physiological systems. Studies have shown that chronic stress, the main environmental risk factor leading to MDD, can promote immune system dysregulation and recruitment of immune cells and deleterious inflammatory mediators to the central nervous system. In this line, the blood-brain-barrier (BBB) maintains a privileged brain environment restricting entry of peripheral inflammatory cytokines and immune cells into the brain, however, its integrity is compromised in human MDD and mice characterized by depression-like behaviors. Importantly, most individuals exposed to stressful events of life remain resilient and do not develop MDD. Accordingly, stress-resilient mice display intact BBB integrity and low inflammatory profile when compared to stress-susceptible animals. Physiology of the brain endothelial cells includes transporters that are involved in the bidirectional flow of macromolecules through this barrier, a mechanism named transcytosis. These transporters maintain BBB integrity and control transcytosis keeping it at physiological level, a mechanism that could be disrupted by chronic stress leading to increased passage of inflammatory markers into the brain. Here, we evaluated expression of endothelial cell transporters in the nucleus accumbens (NAc) of C57Bl6 mice, an important brain area involved in mood regulation and hedonic behavior. Mice were subjected to 10-day chronic social defeat stress followed by social interaction test 24h later to determine behavioral phenotype. Then, NAc punches were collected and gene level expression quantified by qPCR. We observed specific gene expression patterns associated to stress susceptibility vs resilience. We are currently confirming validity of our mouse findings in post-mortem tissue from depressed patients which will add translational value to this research. The BBB is perfectly located to bridge peripheral immune communication to the brain neuronal circuits. My project will shed a new light on the biology of emotions by deciphering how the peripheral immune system interacts with the brain neurovasculature to modify neuronal circuits involved in emotional processing.