A series of discoveries spanning the last decade has challenged our view of microglia, the brain’s innate immune cells, showing their essential but previously unexpected contribution to the remodeling of neuronal circuits. In this emergent field of investigation, research in Dr. Marie-Eve Tremblay’s laboratory at the Division of Medical Sciences, University of Victoria, aims to determine how this newly-defined mechanism could be implicated in the loss of neuronal connections that best correlates with the impairment of learning and memory across major depression, schizophrenia, aging, and neurodegenerative diseases.
The goal of our research is to design novel therapeutic strategies that specifically target microglia to promote brain resilience and healthy cognitive functions along the aging trajectory. We thereby aim to prevent and treat major depressive disorder, schizophrenia, and the highly prevalent sporadic forms of neurodegenerative diseases that include Parkinson’s and Alzheimer’s.
Microglia emerged since 2005 and especially 2010 as key players in brain development, maturation, function, plasticity, and integrity, across contexts of health and disease, sexes, and stages of life. In 2016, our ultrastructural analyses defined the dark microglia (DM), a state strikingly different from the other ones described so far. DM are distinguished by their unique combination of cellular stress markers: condensation of cytoplasm and nucleoplasm (giving them a dark appearance), mitochondrial alteration, endoplasmic reticulum and Golgi apparatus dilation, and loss of microglial heterochromatin patterning. Rare in healthy young adult mice, DM become prevalent upon exposure to maternal immune activation (using the viral mimic Poly I:C or a Western diet), chronic stress, loss of fractalkine signaling between neurons and microglia, aging, Huntington’s and Alzheimer’s disease pathology, where they reach 40% of the microglial population. These findings support the view that “multitasking” microglia constitute a diverse population, composed of subtypes each exerting specialized functions.
While the biological relevance of transcriptionally-defined disease-associated microglial subtypes remains largely elusive, we recently identified a set of common features between these cells and DM. Moreover, we made significant advances in our understanding of DM’s metabolic state and functional relationships within the brain. DM’s ensheathment of the vasculature, satellite positions onto neurons and other glial cells, and extensive interactions with synapses–phagocytic and non-phagocytic–lead us to propose that DM play crucial roles in vascular and synaptic remodeling. Furthermore, DM uniquely display a high prevalence of glycogen granules indicating a metabolic difference compared to the other microglia. Our work is currently investigating how DM’s actions could be initially beneficial (e.g., during development), but become detrimental in contexts of stress-induced plasticity, aging and diseases. Innovative therapies targeting DM and their effector functions hold the potential to preserve cognitive functions upon exposure to various challenges throughout life.
Leadership & Outreach
Dr. Marie-Ève Tremblay’s work revealed that microglia, which are the brain’s immune cells, actively remodel neuronal circuits during normal physiological conditions. Her original discovery, published in PLoS Biology (Tremblay et al., 2010), was cited 1281 times (Google Scholars). It was recommended by Faculty of 1000, publicized twice in Nature, and presented to the public in New Scientist and Médecine/Sciences. Her follow-up work in GLIA (Tremblay et al., 2012) was also influential, with 261 citations received. These findings stimulated the development of a new field of research investigating the roles of microglia in the healthy brain. The mini-symposium “The role of microglia in the healthy brain” that she organized and chaired at the 2011 Society for Neuroscience meeting contributed to the launch of this new field, was attended by 800+ participants, and resulted in a publication in The Journal of Neuroscience cited 906 times.
As an independent investigator, she has identified fractalkine signaling as an important neuron-microglia pathway that underlies stress-induced cognitive impairment. This work resulted in a co-senior author publication in Brain Behavior and Immunity (Milior et al., 2016; 171 citations) that was selected for the journal’s cover page. It was preceded by a review article in Frontiers in Cellular Neuroscience cited 253 times (Paolicelli et al., 2014). At the same she has identified “dark microglia” as a microglial subset rare in healthy adult mice that becomes highly prevalent upon chronic stress, aging, fractalkine signaling deficiency, and Alzheimer’s disease pathology. This work published in GLIA (Bisht et al., 2016) was cited 259 times and notably discussed in the New Scientist. Her follow-up work further uncovered these cells following maternal immune activation (induced by viral infection), considered a main risk factor for neurodevelopmental disorders, and in Huntington’s disease pathology (Hui et al., 2018 Frontiers in Cellular Neuroscience and Savage et al., 2020 Journal of Neuroinflammation, respectively cited 98 times and 30 times). These findings which were notably discussed in a review article in Neurobiology of Stress cited 190 times (Bisht et al., 2018) revealed that dark microglia contribute to the pathological remodeling of neuronal circuits, across stress-induced plasticity, aging, and in various disease conditions. This research into dark microglia is expected to provide novel therapies specifically targeting the microglial subset implicated in synaptic loss and cognitive decline. This work is at the heart of her Tier II Canada Research Chair in Neurobiology of Aging and Cognition research program.
Supporting the importance of this research, Dr. Tremblay was ranked among the 1% most highly cited researchers in her field by Clarivate in 2021 (with 6 other Faculty at the University of Victoria). She was also ranked 3rd World Microglial Expert by Expertscape for 85 eligible papers cited between 2011 and 2021. Her career goal is to become a world leader in the development of innovative therapies normalizing microglial functions upon the exposure to various environmental risk factors for disease throughout life. Her independent research funding has included so far 20 research grants, 10 as a principal investigator, 1 as a co-principal investigator, 8 as a co-investigator, and 1 as a project partner, in addition to a research contract with Med-Life Discoveries LP as a principal investigator. She has also received 3 Canada Foundation for Innovation Leaders Grants to acquire cutting-edge microscopy systems specially customized for the study of neuroimmune interactions. Her expertise is internationally recognized. With her diverse research team which has included over 75 trainees from high school, college, undergraduate, graduate, and postdoctoral levels, as well as research technicians and assistants, she has contributed to several collaborative studies in the fields of neuroscience, reproduction, nutrition, (immuno)metabolism, and immunology (e.g., published in Cell, Nature Methods, Science Translational Medicine, Journal of Clinical Investigation, Journal of Experimental Medicine, Cell Reports, Nature Neuroscience, PLoS Biology, eLife, Communications Biology, PNAS). She was invited to present her work 124 times, as seminars, lectures at symposia, specialized courses, and meetings. She has 150 publications that were cited 9,041 times, corresponding to an h-index of 44 and an i10-index of 93 (Google Scholar). Despite the pandemic, she has had her most productive years so far since moving to Victoria, with 23 manuscripts published in 2020, 28 manuscripts published in 2021, and 15 published or in press since the beginning of 2022.
Marie-Ève Tremblay, Ph.D.
Haley Vecchiarelli, Ph.D.
Ifeoluwa O. Awogbindin, Ph.D.
I crossed path with Dr. Marie-Eve Tremblay in December 2018 during an IBRO Advanced School on Neuroimmunology and Gut Brain Axis in South Africa. I joined the lab in August 2019, having won the IBRO-African Regional Committee Bursary. My project aims to determine the implications of microglia as well as the contributions of oligodendrocytes to the progression of Parkinson’s disease.
Elizabeth Olonode-Akinluyi, Ph.D.
Luana Tenorio-Lopes, Ph.D.
I officially joined Dr. Marie-Eve Tremblay’s laboratory as a Ph.D. student in fall 2020 following up on my internship in the previous year. My thesis project will focus on characterizing microglial changes along the aging trajectory. Older age-associated microglial variability will be further investigated in the context of susceptibility to infectious diseases and related consequences on cognitive functioning.
I began my masters with Dr. Marie-Eve Tremblay in the spring of 2017. Since first joining her laboratory in May 2016, I have studied the roles of microglia in various contexts including Parkinson’s and Huntington’s disease. I am now investigating, in my Ph.D. project, the role of different microglial subtypes including the dark microglia in development, aging and Alzheimer’s disease.
I began my master's project in 2017 with Dr. Marie-Eve Tremblay. I studied the role of glucocorticoid receptors expressed by microglia in the response of the brain and behaviour to chronic unpredictable stress. I am now investigating, in my Ph.D. thesis with Dr. Marie-Eve Tremblay, the role of microglia-synapse interactions in the regulation of sleep.
Fernando González Ibáñez
I joined the laboratory in January 2017. My Ph.D. project supervised by Dr. Marie-Eve Tremblay focuses on the impact of two environmental risk factors for disease (cigarette smoking, chronic psychological stress) on the brain and behaviour. My work focuses on microglia and their involvement in the remodeling of neuronal circuits as an underlying mechanism driving cognitive alteration.
I began my doctoral degree in the summer of 2019. My project focuses on the origin of dark microglia (from the embryonic yolk sac or bone marrow) and characterizes, using a transgenic mouse model, the interactions of bone marrow-derived myeloid cells at synapses, with interest in applying this model to study schizophrenia. I am currently the trainee in charge of our laboratory's two-photon experiments.
Victor Lau, M.Sc.
Elisa Gonçalves de Andrade
I joined the laboratory of Dr. Marie-Eve Tremblay in September 2020, when starting my Masters in Neuroscience at the University of Victoria. My project investigates the effects of focused ultrasound stimulation on the ultrastructure of the neurovascular unit (astrocytes, microglia, pericytes, endothelial cells, perivascular macrophages, basement membrane, etc.) in mice.
Bianca Caroline Bobotis
I started my honours program in Dr. Tremblay’s lab in the fall of 2020. My project is looking at the effects of vaporized cannabinoids on microglia acutely in the prefrontal cortex of mice. I will analyze microglial density, distribution and morphology to understand their physiological functions that are necessary for homeostasis and neuroprotection. Additionally, I will be looking at microglia’s ultrastructural features to understand their interactions with synapses.
From left to right: Marie-Kim St-Pierre, Victor Lau, Eva Šimončičová, Katherine Picard, Elisa Gonçalves de Andrade, Fernando González Ibáñez, Marie-Ève Tremblay, Jared VanderZwaag, Mohammadparsa Khakpour, Sophia Loewen, Chloe McKee, Micaël Carrier, Haley Vecchiarelli, Benneth Ben-Azu
From left to right: Maude Bordeleau, Charlotte Noël, Cyril Bolduc, Julie Savage, Micaël Carrier, Marie-Ève Tremblay, Fernando González Ibáñez, Nathalie Vernoux, Amin Benadjal, Marie-Kim St-Pierre, Marie-Ève Robert
From left to right: Hassan El Hajj, Julie Savage, Kaushik Sharma, Nathalie Vernoux, Julien Blouin, Marie-Ève Tremblay, Fernando González Ibáñez, Cynthia Lecours, Katherine Picard, Marie-Kim St-Pierre, Maude Bordeleau, Kanchan Bisht, Micaël Carrier, Geneviève Parent
From left to right: Nathalie Vernoux, Kanchan Bisht, Kaushik Sharma, Marie-Kim St-Pierre, Abygaël St-Pierre, Marie-Ève Tremblay, Clémentine Beucher, Cynthia Lecours, Hassan El Hajj, Julie Savage, Chin Wai (Thomas) Hui, Micaël Carrier, Mathilde Henry
Additional lab members: Fanny Decoeur, Lisa Scheefhals, Constantin Delmas, Doriane Pouliot, Rosalie Buteau-Poulin, Véronique Fournier, Gabrielle Duvoisin de Soumagnat, Audrey Gagné, Jérôme Detuncq, Julien Blouin, Geneviève Parent, Moritz Ferch, Éloi Gagnon, Alexie Doucet, Maude Bordeleau, Fernando González Ibáñez, Sammy Weiser Novak
From left to right: Cynthia Lecours, Kanchan Bisht, Isabelle Girard, Julie Savage, Oihane Abiega, Marie-Ève Tremblay, Mathilde Henry, Nathalie Vernoux, Valerio Messina
Additional lab members: Samuel Boisjoly-Villeneuve, Philippe LeBrun, Audray Maude Baril-Lecompte, Julie Bremond, Marika Mercier, Jessika Landry-Morneau, Alexandra Cayouette, Kim Larose-Labrecque, Louis Samson, Danaja Plevel, Steven Gagnon, Yvan Rémy, Marie-Kim St-Pierre, Abygaël St-Pierre, Katherine Picard, Clémentine Beucher, Micaël Carrier, Hassan El Hajj, Maude Bordeleau, Chin Wai (Thomas) Hui, Kaushik Sharma
From left to right: Kanchan Bisht, Louis Samson, Marie-Ève Tremblay, Hassan El Hajj, Cynthia Lecours, Maria Gabriela Sanchez
Additional lab members: Samuel Comeau, Mathilde Henry, Samuel Boisjoly-Villeneuve
News & Events
2022 – Canadian Institutes of Health Research (CIHR) graduate student award – master to Victor Lau
2022 – BranchOut Neurological Foundation Scholarship to Sophia Loewen
2022 – Boehm Family Award for Excellence in Science at the Faculty of Science Honours Fest- 2nd Place Poster Award to Chloe McKee
2022 – Doctoral training scholarship from Fonds de recherche du Québec – Santé (FRQS) to Marie-Kim St-Pierre
2021 – Doctoral training scholarship from FRQS to Micaël Carrier
2021 – BranchOut Neurological Foundation Scholarship to Eva Simoncicova
2021 – Canadian Institutes of CIHR graduate student award – master to Jared VanderZwaag
2021 – International Brain Research Organization (IBRO) Bursary Postdoctoral Fellowship to Benneth Ben-Azu
2021 – Natural Sciences and Engineering undergraduate summer award to Torin Halvorson
2021 – Biology Summer Undergraduate Research Award (SURA) and Division of Medical Sciences Jamie Cassels Undergraduate Research Award (JCURA) to Chloe McKee
2021– Ranking among the 1% most highly cited researchers by Clarivate in 2021 (with 6 other Faculty at the University of Victoria) for Dr. Tremblay
2021 – 3rd World Microglial Expert ranking by Expertscape for 85 eligible papers cited between 2011 and 2021 for Dr. Tremblay
2020 – Research trainee award from the Michael Smith Foundation for Health Research to Haley Vecchiarelli
2020 – Semi-finalist position at the BioRender Graphical Abstract Contest to Ifeoluwa O. Awogbindin
2020 – International Brain Research Organization – African Regional Committee (IBRO-ARC) award to Ifeoluwa O. Awogbindin
2020 – IBRO international travel grant to attend the International Society for Neurochemistry (ISN)-American Society for Neurochemistry (ASN) meeting in Montréal, Québec to Ifeoluwa O. Awogbindin
2020 – ISN Committee for Aid and Education in Neurochemistry Award to Elizabeth Olonode-Akinluyi
2020 – Faculty of graduate studies (FGS) entrance award from University of Victoria to Elisa Gonçalves de Andrade
2020 – FGS entrance award from University of Victoria to Eva Šimončičová
2020 – Postdoctoral fellowship from the Canadian Institutes of Health Research (CIHR) to Haley Vecchiarelli
2020 – Doctoral training scholarship from Fond de Recherche du Québec – Santé (FRQS) to Katherine Picard
2020 – Excellence scholarship from Centre thématique de recherches en neurosciences (CTRN) of Université Laval to Katherine Picard
2019 – Doctoral training scholarship from FRQS to Marie-Kim St-Pierre
2019 – 2nd place at ‘My thesis in 180 seconds’ contest from the Neuroscience Axis at Centre de recherche du CHU de Québec-Université Laval to Micaël Carrier
2019 – Frederick Banting and Charles Best Canada doctoral training scholarship from CIHR to Marie-Kim St-Pierre
2019 – Young Investigator Training Program award from the International Brain Research Organization (IBRO) to attend the 10th IBRO World Congress of Neuroscience in Daegu, South Korea to Maude Bordeleau
2019 – Travel award Citoyens du Monde – Fondation Famille-Choquette from Université Laval to Katherine Picard
2019 – Travel award for the ISN-ASN meeting in Montréal, Québec to Ifeoluwa O. Awogbindin
2019 – Travel award for the ISN-ASN meeting in Montréal, Québec to Maude Bordeleau
2019 – Travel award for the ISN-ASN meeting in Montréal, Québec to Marie-Kim St-Pierre
2019 – Travel award for the ISN-ASN meeting in Montréal, Québec to Micaël Carrier
2019 – Travel award for the ISN-ASN meeting in Montréal, Québec to Fernando González Ibáñez
2019 – Travel Award for the XIV European Meeting on Glial Cells in Health and Disease – Network GLIA to Maude Bordeleau
2019 – Albert-Aguayo Award from the Integrated Program in Neuroscience at McGill University to Maude Bordeleau
2019 – Neuroscience Axis scholarship from Centre de recherche du CHU de Québec-Université Laval to Cyril Bolduc
2018 – Trainee professional development Award (TPDA) from Society for Neurosciences to Marie-Kim St-Pierre
2018 – Canada neuroimmunology knowledge dissemination award from the International Society of Neuroimmunology to Marie-Kim St-Pierre
2018 – Scientific communication excellence award from the Molecular Medicine Department of Université Laval to Katherine Picard
2018 – Scientific communication excellence award from the Molecular Medicine Department of Université Laval to Micaël Carrier
2018 – Excellence scholarship from the Association des chercheuses et chercheurs étudiant à la Faculté de Médecine (ACCEM) of Université Laval to Micaël Carrier
2018 – Excellence scholarship from the ACCEM of Université Laval to Marie-Kim St-Pierre
2018 – Excellence scholarship from the ACCEM of Université Laval to Katherine Picard
2018 – Prix Diamant recherche – relève category from the CHU de Québec-Université Laval to Marie-Ève Tremblay
2018 – GREAT travel award from the Integrated Program in Neuroscience at McGill University to Maude Bordeleau
2018 – Undergraduate student research award from the Natural Sciences and Engineering Research Council of Canada (NSERC) to Julien Blouin
2018 – Travel award for the Stress Neurobiology Workshop 2018 Meeting to Micaël Carrier
2018 – Master training award from FRQS to Marie-Kim St-Pierre
2018 – Master training award from FRQNT to Marie-Kim St-Pierre
2018 – Master training award from FRQS to Micaël Carrier
2018 – Master training award from FRQNT to Micaël Carrier
2018 – Master training award from CIHR to Marie-Kim St-Pierre
2018 – Tenacity scholarship from Faculty of Medicine at Université Laval to Kanchan Bisht
2018 – Travel award from the Canadian Association for Neuroscience (CAN-CAN) to Micaël Carrier
2017 – Entrance excellence scholarship from Faculty of Medicine at Université Laval to Micaël Carrier
2017 – Excellence scholarship from the Molecular Medicine Department of Université Laval to Marie-Kim St-Pierre
2017 – Excellence scholarship from the Fondation du CHU de Québec to Katherine Picard
2017 – Excellence scholarship from the Fondation du CHU de Québec to Marie-Kim St-Pierre
2017 – Admission excellence scholarship from Faculty of Medicine at Université Laval to Marie-Kim St-Pierre
2017 – Doctoral training award from FRQS to Maude Bordeleau
2017 – Postdoctoral training award from FRQS to Julie Savage
2017 – Postdoctoral training award from FRQS to Chin Wai (Thomas) Hui
2017 – Excellence scholarship from Fédération des caisses Desjardins du Québec to Audrey Gagné
2017 – First-author publication award from Faculty of Medicine at Université Laval to Kanchan Bisht
2017 – Travel award from the ACCEM of Université Laval to Kanchan Bisht
2017 – Undergraduate student research award from NSERC to Jérôme Detuncq
2017 – Undergraduate student research award from NSERC with supplement from FRQNT to Marie-Kim St-Pierre
2016 – Claude-Fortier award for academic excellence and implication in the Biomedical Sciences program of Université Laval to Micaël Carrier
2016 – Best poster award at Journée Phare, Bromont, Québec to Mathilde Henry
2016 – Travel award Marie Giguère from Fondation Douglas to Maude Bordeleau
2016 – Travel award from the ACCEM of Université Laval to Mathilde Henry
2016 – Excellence scholarship (Bourse Didier-Mouginot) from the Fondation du CHU de Québec to Cynthia Lecours
2016 – Excellence scholarship from Fondation du CHU de Québec to Kanchan Bisht
2016 – Excellence scholarship from the Molecular Medicine Department to Cynthia Lecours
2016 – Excellence scholarship from the Molecular Medicine Department to Kanchan Bisht
2016 – Master training award from FRQS to Cynthia Lecours
2016 – Undergraduate student research award from NSERC to Cynthia Lecours
2015 – Best poster award at the Neuroscience Day of Université Laval to Julie Savage
2015 – Travel award for the Americas School of Neuroimmunology in Calgary to Hassan El Haj
2015 – Scholarship from the Lebanese Ministry of Education and Higher Education to Hassan El Hajj
2015 – Scholarship from the Indo-Canadian Shastri Foundation to Kanchan Bisht
2015 – Travel Award from the National Institute of Neurological Disorders and Stroke to Kanchan Bisht
2015 – Undergraduate student research award from NSERC to Isabelle Girard
Your suggestions and comments are most welcome !