One out of every five people will suffer from major depressive disorder (MDD) in their lifetime. The World Health Organization recently reported that MDD is now the major cause of disability and affects over 300 million people. Symptoms of MDD include recurrent depressive episodes, irritability, loss of interest for previously pleasurable activities, difficulties concentrating and disturbed appetite and sleep habits.

Clinical studies revealed higher prevalence of MDD in patients suffering from diseases including an inflammatory component such as cardiovascular diseases (17-27%) and Alzheimer’s disease (AD, 30-50%) (Menard et al., Neuropsychopharmacology, 2017). Underscoring these data is the finding that subsets of MDD patients display exacerbated immune responses (Hodes et al., Nature Neuroscience, 2015). Chronic stress is associated with neurovascular and neuroimmune changes and it is possible that individual differences in these adaptations underlie resilience versus vulnerability to stress and the establishment of MDD symptoms. However to date the mechanisms by which these systems interact with the brain to induce maladaptive behaviors remain largely unknown.

Thus, I will explore this question by investigating how chronic stress affects the blood-brain barrier (BBB) (Menard et al., Nature Neuroscience, in press). The BBB represents the ultimate frontier between the brain and deleterious peripheral immune signals. I will combine molecular, morphological, functional and behavioral techniques to decipher the role of BBB function and metabolism and neurovascular health in the development of MDD. I will also apply these approaches to a mouse model of AD. Higher prevalence of MDD in AD patients may be related to enhanced BBB permeability and infiltration of immune signals leading to neurodegeneration.

The strength of my approach is a reverse translational strategy that consists in studying stress response in mice to unravel novel biological mechanisms underlying MDD and AD in humans. By understanding how chronic stress affects the BBB we may be able to augment current antidepressant treatment or design new therapeutic strategies targeting patients suffering from neurodegenerative diseases.

My research program will combine behavioral experiments to functional, molecular and imaging studies and validate rodent findings in human samples to provide translational value to our basic research projects. The role of microbiome on cardiovascular health and the establishment of mood disorders will be actively investigated in the context of the Sentinel North Junior Research Chair. These studies will be perform in collaboration with researchers and clinicians already involved in the Sentinel North initiative.