Caroline Ménard,
PhD

Assistant Professor, Department of Psychiatry and Neurosciences, Faculty of Medicine, Université Laval

Sentinel North Junior Research Chair

Research Interests

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.

Key Publications

https://www.ncbi.nlm.nih.gov/myncbi/browse/collection/47662464/?sort=date&direction=descending

Menard, C, Pfau, ML, Hodes, GE, Kana, V, Wang, VX, Bouchard, S, Takahashi, A, Flanigan, ME, Aleyasin, H, LeClair, K, Janssen, WG, Labonté, B, Parise, E, Lorsch, ZS, Golden, SA, Heshmati, M, Tamminga, C, Turecki, G, Campbell, M, Fayad, Z, Tang, CY, Merad, M, Russo, SJ (2017) Social stress induces neurovascular pathology promoting depression, Nature Neuroscience, in press.
Hodes, GE, Kana, V, Menard, C, Merad, M, Russo, SJ (2015) Neuroimmune mechanisms of depression, Nature Neuroscience, 18(10), 1386-1393.
Menard, C, Pfau, ML, Hodes, GE, Russo, SJ (2017) Immune and Neuroendocrine Mechanisms of Stress Vulnerability and Resilience, Neuropsychopharmacology, 42(1), 62-80.
Labonté B, Engmann, O, Purushothaman, I, Menard, C, Wang, J, Tan, C, Scarpa, JR, Moe, G, Loh, E, Cahill, M, Lorsch, ZS, Hamilton, PJ, Calipari, ES, Hodes, GE, Issler, O, Kronman, H, Pfau, M, Obradovic, A, Dong, Y, Neve, R, Russo, SJ, Kazarskis, A, Tamminga, C, Mechawar, N, Turecki, G, Zhang, B*, Shen, L*, Nestler, EJ* (2017) Sex-Specific Transcriptional Signatures in Human Depression, Nature Medicine, 23(9), 1102-1111.
Golden, SA, Heshmati, M*, Flanigan, M*, Christoffel, DJ, Guise, K, Pfau, ML, Aleyasin, H, Menard, C, Zhang, H, Hodes, GE, Bregman, D, Khibnik, LA, Tai, J, Rebusi, N, Krawitz, B, Chaudhury, D, Walsh, JJ, Han, MH, Shapiro, ML, Russo, SJ (2016) Basal forebrain projections to the lateral habenula modulate aggression reward, Nature, 534, 688-692.
Pfau, ML*, Menard, C*, Russo SJ (2018) Inflammatory Mediators in Affective Disorders: Therapeutic Opportunities, Annual Review of Pharmacology and Toxicology, in press.
Takahashi, A, Chung, JR, Zhang, S, Zhang, H, Grossman, Y, Aleyasin, H, Flanigan, M, Pfau, ML, Menard, C, Dumitriu, D, Hodes, GE, McEwen, BS, Nestler, EJ, Han, MH, Russo, SJ, Establishment of repeated social defeat stress model in female C57BL/6 mice, Scientific Reports, 7(1): 12838.
Menard, C, Hodes, GE, Russo, SJ (2016) Pathogenesis of depression: insights from human and rodent studies, Neuroscience, Special Issue Animal Models of Neuropsychiatric Disease, 321, 138-162. Figure 2 selected for the cover of Neuroscience journal issue 321.
Hodes, GE, Pfau, ML, Purushothaman, I, Ahn, HF, Golden, SA, Christoffel, DJ, Magida, J, Brancato, A, Takahashi, A, Flanigan, ME, Menard, C, Aleyasin, H, Koo, JW, Lorsch, J, Feng, J, Heshmati, M, Wang, M, Turecki, G, Neve, R, Zhang, B, Shen, L, Nestler, EJ, Russo, SJ (2015) Sex differences in nucleus accumbens transcriptome profiles associated with susceptibility versus resilience to sub-chronic variable stress, The Journal of Neuroscience, 35(50), 13362-13376.
Jiang, C, Lin, WJ, Sadahiro, M, Labonté, B, Menard, C, Pfaul, ML, Tamminga, CA, Turecki, G, Nestler, EJ, Russo, SJ, Salton, SR (2018) VGF function in depression and antidepressant efficacy, Molecular Psychiatry, in press.
Menard, C, Quirion, R, Vigneault, E, Bouchard, S, Ferland, G, El Mestikawy, S, Gaudreau, P (2015) Glutamate presynaptic vesicular transporter and postsynaptic receptor levels correlate with spatial memory in aging rat models, Neurobiology of Aging, 36(3), 1471-1482.
Menard, C, Tse, YC, Cavanagh, C, Chabot, JC, Herzog, H, Schwarzer, C, Wong, TP, Quirion, R (2013) Knockdown of prodynorphin gene prevents cognitive decline, reduces anxiety and rescues loss of group 1 mGlu receptor function in aging, The Journal of Neuroscience, 33(31), 12792-12804.
Farso, MC, Menard, C, Colby-Milley, J, Quirion, R (2013) The immune marker CD68 correlates with cognitive impairment in normally aged rats, Neurobiology of Aging, 34(8), 1971-1976.
Menard, C, Quirion, R (2012) Group 1 metabotropic glutamate receptor function and its regulation of learning and memory in the aging brain, Frontiers in Pharmacology, Research topic, mGluRs: Reinforcement, Extinction, Incentive Learning and Protein Interactions, 3, 182.
Menard, C, Quirion, R (2012) Successful Cognitive Aging in Rats: A Role for mGluR5 Glutamate Receptors, Homer 1 Proteins and Downstream Signaling Pathways, PLoS One, 7(1), e28666.

Short Biography

I will join the Department of Psychiatry and Neuroscience at the Faculty of Medicine, Université Laval (Quebec City, Canada) as an Assistant Professor and open my lab in the Neurophotonics Centre at the CERVO Brain Research Center in February 2018.

I was a postdoctoral fellow in Scott Russo's laboratory, Center for Affective Neuroscience at the Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, USA for 3 years. I led projects investigating the neurobiology of stress vulnerability and resilience and the development of mood disorders.

In my previous academic positions at the Université de Montréal CRCHUM, Douglas Hospital Research Center affiliated with McGill University and Universite du Quebec at Trois-Rivieres, I investigated the neurobiology of learning and memory, diet-induced brain plasticity, aging and Alzheimer's disease.

I also worked in industry as a R&D scientist (supported by NSERC) and developed protocols to reprogram human stem cells in neurons and evaluated their properties at the morphological and functional levels.

I have a broad background in neuroscience, psychiatric disorders and behavioral studies with specific training and expertise in brain plasticity, stress response, neurovascular health, immunology, cell biology and molecular biology/epigenetics.