Martin Lévesque, Ph.D.
Professor
Department of psychiatry and neurosciences
Université Laval
Research into the causes of Parkinson's disease aiming to develop new treatments
Professor Martin Lévesque studies the development and maintenance of neural circuits that produce dopamine in the brain. His research has identified molecules that are necessary for the development, survival and integration of dopaminergic neurons in the brain. These neurons play a crucial role in movement control, mood, attention and stress response.
Dr. Lévesque's research has led to important advances in the understanding of Parkinson's disease, a neurodegenerative disease characterized by progressive death of dopaminergic neurons. Deficiencies in the function or integration of dopamine neurons are also at the origin of other brain diseases such as schizophrenia, attention disorders and even depression.
Dr. Lévesque's team has recently shown that two factors, named Lmx1a and Lmx1b, are essential for the survival of dopaminergic neurons, since they control the production of energy necessary for their functioning. They were able to show that inactivation of these factors recreates the cellular characteristics observed in Parkinson's disease. These studies have shown a link between defects in energy production in cells, the development of Parkinson-specific traits, and the death of dopamine neurons. The factors Lmx1a and Lmx1b also play a role in the development of dopamine neuronal networks during embryonic development.
The characterization of the role of several genes by the Lévesque laboratory aims in the long run to develop therapies to protect neurons from degeneration and possibly to regenerate neural circuits from stem cells.
MIDBRAIN DOPAMINERGIC NEURONS AND BRAIN DISEASES
Midbrain dopamine neurons play crucial roles in the control of a variety of brain functions, including voluntary movements, mood, reward, attention and stress. Dysfunction or abnormal development of these neurons is responsible for many brain disorders such as schizophrenia, attention deficit as well as depression. Degeneration of midbrain dopamine neurons is also the primary cause of Parkinson’s disease, a major human neurological disorder.
Very little is known about how dopamine axons find their targets during development or the factors that contribute to their maintenance in the adult brain. The goal of our laboratory is to understand the cellular and molecular mechanisms regulating the development and maintenance of dopaminergic neuronal circuits. More specifically, our research projects aim to:
1) Elucidate the roles transcription factors during embryonic development and in
adult brain.
2) Identify and define the function of the molecules that regulate axon guidance and
proper innervation of dopaminergic neurons to their specific targets.
3) Apply our fundamental discoveries to the development of new therapies to protect
dopamine neurons from degeneration and to develop efficient cell replacement
therapy to regenerate dopaminergic circuits from stem cells.
RESEARCH ASSISTANTS
Véronique Rioux, M.Sc.
Modesto Peralta, B.Sc.
PH.D. STUDENTS
Axelle Dovonou
Anne-Marie Castonguay
Charles Gora
Victoria Soto
M.SC. STUDENTS
Cyril Bolduc
Owen Ferguson
POSTDOCTORAL FELLOW
Tiago Cardoso
Julia Obergasteiger
Quessy F, Thibault B, Blanchette LJ, Lévesque M*, Labonté B* (2021) Stress-induced alterations of mesocortical and mesolimbic dopaminergic pathways. Scientific Reports, 2021 May 26;11(1):11000. doi: 10.1038/s41598-021-90521-y. *Co-corresponding author
Goulding S, Lévesque M, Sullivan AM, Collins LM, O’Keeffe GW. (2021) Quinacrine and Niclosamide promote neurite growth in midbrain dopaminergic neurons through the canonical BMP-Smad pathway and protect against neurotoxin and alpha-synuclein-induced neurodegeneration. Molecular Neurobiology, 2021 Jul;58(7):3405-3416. doi: 10.1007/s12035-021-02351-8. Epub 2021 Mar 12.
Castonguay AM, Gravel C and Lévesque M. (2020) Treating Parkinson’s disease with antibodies: previous studies and future directions. Journal of Parkinson Disease, 2021;11(1):71-92. doi: 10.3233/JPD-202221.
Goulding S, Concannon R, Morales Prieto N, Villalobos-Manriquez F, Clarke G, Collins LM, Lévesque M, Wyatt SL, Sullivan AM, O’Keeffe GW. (2020) Growth differentiation factor 5 exerts neuroprotection in an α-synuclein rat model of Parkinson's disease, Brain, 2020 Nov 30;awaa367. doi: 10.1093/brain/awaa367.
Gilmozzi V, Gentile G, Castelo-Rueda MP, Hicks AA, Pramstaller P, Zanon A, Lévesque M and Pichler I. (2020). Interaction of alpha-synuclein with membranes: mitochondrial cardiolipin as a critical player in the pathogenesis of Parkinson’s disease. Frontier in Neuroscience, 14:578993. doi: 10.3389/fnins.2020.578993.
Awatramani R, Lévesque M (2020). ‘‘The One Who Guides’’ Nigral Neuron Migration. Neuron, preview 107(443): 595-596.
Cardoso T, Lévesque M. (2020). Toward Generating Subtype-Specific Mesencephalic Dopaminergic Neurons in vitro. Frontier in Cell and Developmental Biology. 2020. 17 June, https://doi.org/10.3389/fcell.2020.00443.
Salesse C, Charest J, Doucet-Beaupré H, Castonguay AM, Labrecque S, De Koninck P and Lévesque M (2020) Opposite control of excitatory and inhibitory synapse formation by Slitrk2 and Slitrk5 on midbrain dopaminergic neurons modulates hyperactivity-related behavior. Cell Report 2020 30 (7):P2374-2386. E5, doi.org/10.1016/j.celrep.2020.01.084.
Gan-Or Z, Rao T, Leveille E, Degroot C, Chouinard S, Cicchetti F, Dagher A, Das S, Desautels A, Drouin-Ouellet J, Durcan T, Gagnon JF, Genge A, Karamchandani J, Lafontaine AL, Sun SLW, Langlois M, Levesque M, Melmed C, Panisset M, Parent M, Poline JB, Postuma RB, Pourcher E, Rouleau GA, Sharp M, Monchi O, Dupré N, Fon EA. (2020) The Quebec Parkinson Network: A Researcher-Patient Matching Platform and Multimodal Biorepository. J Parkinsons Dis. 2020;10(1):301-313. doi: 10.3233/JPD-191775.
Ben Yousef S, Brisson G, Doucet-Beaupré H, Castonguay AM, Gora C, Amri M, Lévesque M. (2019). Neuroprotective effect of grape seed and skin extract against 6-OHDA toxicity in dopaminergic neurons. Nutritional Neuroscience. May 25: 1-15.
Sanz RL, Ferraro GB, Kacervosky J, Salesse C, Gowing E, Beaubien F, Rambaldi I, Holmbeck K, Cloutier JF, Lévesque M, Murai K and Fournier AE. (2017). MT3-MMPpromotes excitatory synapse formation by promoting Nogo-66 receptor ectodomain shedding. Journal of Neuroscience 2017 Dec 1. pii: 0962-17. doi: 10.1523/JNEUROSCI.0962-17.2017.
Chabrat A, Brisson G, Doucet-Beaupré H, Salesse C, Profes MS, Dovonou A, Akitegetse C, Charest J, Lemstra S, Cote D, Pasterkamp RJ, Abrudan M, Metzakopian E, Ang SL, Lévesque M. (2017). Lma1a and Lmx1b regulate PlexinC1 expression and axon targeting of midbrain dopamine neurons. Nature Communications. Oct 16;8(1):933. doi: 10.1038/s41467-017-01042-0.
Khan S, Stott SRW, Chabrat A, Truckenbrodt A, Spencer-Dene B, Nave KA, Guillemot F, Lévesque M, Ang SL. (2016). Survival of a novel subset of midbrain dopaminergic neurons projecting to the lateral septum is dependent on NeuroD proteins. Journal of Neuroscience. 37(9): 2305-2316.
Verwey M, Grant A, Meti N, Adye-White L, Torres-Berrío A, Rioux V, Lévesque M, Charron F, Flores C. (2016). Mesocortical Dopamine Phenotypes in Mice Lacking the Sonic Hedgehog Receptor Cdon. eNeuro 0009-16.2016.
Doucet-Beaupre H, Gilbert H, Profes MS, Chabrat A,Pacelli C, Giguere N, Rioux V, Charest J, Deng Q,Laguna A, Ericsson J, Perlman T, Ang SL, Cicchetti F, Parent M, Trudeau LE, Lévesque M. (2016). Lmx1a and Lmx1b regulate mitochondrial functions and survival of adult midbrain dopaminergic neurons. Proc Natl Acad Sci U S A. 2016;113(30):E4387-96.
Law C, Profes MS, Levesque M, Kaldschmidt J, Verhage M, Kania A. (2015). Normal molecular specification and neurodegenerative disease-like death of spinal neurons lacking the SNARE- associated synaptic protein Munc18-1. Journal of Neuroscience. 36(2): 561-576.
Doucet-Beaupré H, Ang SL, Lévesque M. (2015). Cell fate determination, neuronal maintenance and disease state: The emerging role of transcription factors Lmx1a and Lmx1b. FEBS Letters. 589: 3727-38.
Cisbani G, Drouin-Ouellet J, Gibrat C, Saint-Pierre M, Lagacé M, Badrinarayanan S, Lavallée-Bourget MH, Charest J,Chabrat A, Boivin L, Lebel M, Bousquet M, Lévesque M, Cicchetti F. (2015) Cystamine/cysteamine rescues the dopaminergic system and shows neurorestorative properties in an animal model of Parkinson's disease. Neurobiology of disease 82, 430-444.
Pacelli C, Giguère N, Bourque MJ, Lévesque M, Slack RS, Trudeau LÉ. (2015). Elevated Mitochondrial Bioenergetics and Axonal Arborization Size Are Key Contributors to the Vulnerability of Dopamine Neurons. Current Biology. 25(18): 2349-60.
Chabrat A*, Doucet-Beaupré H*, Lévesque M. (2015). RNA isolation from cell specific subpopulations using laser-capture microdissection combined with rapid immunolabeling. JOVE. 98(Apr 11): 10.3791/52510. *Co-first.
Pelletier SJ, Lagacé M, St-Amour M, Arsenault D, Fecteau S, Chabrat A, Levesque M, Cicchetti F. (2014). The morphological and molecular changes of brain cells exposed to direct current electric field stimulation. The International Journal of Neuropsychopharmacology. 18(5): 1-16.
Mille F*, Tamayo-Orrego L*, Lévesque M*, Remke M, Korshunov A, Cardin J, Bouchard N, Izzi L, Kool M, Northcott PA, Taylor MD, Pfister SM and Charron F.(2014). The Shh Receptor Boc Promotes Progression of Early Medulloblastoma to Advanced Tumors. Developmental Cell. 31(1): 37-47. *Co-first.
Doucet-Beaupré H, Lévesque M. (2013). The role of developmental transcription factors in adult midbrain dopaminergic neurons. Open Access Neurosciences. 1(1): 1-13.
Yan CH* , Levesque M* , Claxton S , Johnson RL , Ang SL. (2011). Lmx1a and lmx1b function cooperatively to regulate proliferation, specification, and differentiation of midbrain dopaminergic progenitors. The Journal of Neuroscience. 31(35): 12413–12425. *Co-first.
Izzi L*, Lévesque M*, Morin S , Laniel D, Wilkes BC , Mille F , Krauss RS , McMahon AP, Allen BL , Charron F. (2011). Boc and Gas1 each form distinct Shh receptor complexes with Ptch1 and are required for Shh-mediated cell proliferation. Developmental Cell. 20(6): 788-801. *Co-first.
Ph.D. in neurobiology, Université Laval
Postdoctoral fellowship, Institut de recherches cliniques de Montréal (IRCM),
Montréal, Canada, (2006-2008)
Postdoctoral fellowship, National institut for medical research,
Londres, Royaume-Uni (2008-2011)
Research Scholar, Fonds de recherche du Québec – Santé
Dopaminergic circuits
Axon growth and guidance
Parkinson disease
Preclinical target validation
Neuroprotection
Cell replacement therapy
Neurorestauration
iPSC
In vivo and in vitro models of Parkinson's disease
Viral vectors
Light-sheet microscopy
Cellular and molecular neuroscience
2601 Chemin de la Canardière
Québec (Québec)
G1J 2G3
Canada
