Dr. Vincent Prévot, Ph.D
Director of the “Development & Plasticity of the Neuroendocrine Brain” Team, INSERM U1172
Co-Director, International Associated Laboratory NEUROBESE (INSERM U1172, University of Lille 2 – Children’s Hospital Los Angeles, University of Southern California)
Interactions between hypothalamic neuroendocrine systems and peripheral hormones are increasingly thought to play a fundamental role in postnatal brain development, the impairment of which lies at the origin of several major neurological and psychiatric disorders. In addition, over the last few years, evidence has been accumulating for the involvement of central neurohormone imbalances in both the pathophysiology of cognitive disorders, such as certain early-onset dementias, and in the pathophysiology of metabolic and reproductive disorders such as obesity and infertility. Our laboratory examines how chemotropic factors and peripheral hormones (estrogen, leptin, AMH…) impact hypothalamic development and function, as well as the importance of non-neuronal cells (tanycytes, astrocytes and endothelial cells) in this dialogue between the periphery and the central nervous system. It also aims to evaluate how pathological conditions (obesity, diabetes etc.) affect these neurobiological events and, conversely, how the impairment of communication between the brain and the periphery renders the organism prone to developing such conditions (obesity, diabetes, precocious and/or delayed puberty and infertility). Our laboratory brings together in a single setting a wide range of theoretical knowledge and technical expertise in its fields of research and is able to investigate physiological and pathological processes from the molecular and genetic/epigenetic levels to that of human patients, thanks to the close interaction between basic scientists and clinicians. For the excellence of our work, our laboratory has been classified as “remarkable” (the highest “grade” attributed to French research laboratories) by our evaluating bodies in 2014.
Vincent Prevot’s postdoctoral work in the laboratory of S. Ojeda at the Oregon National Primate Research Center/Oregon Health & Science University, USA, continued the study of neuronal and glial plasticity in the GnRH system, crucial for the onset of puberty and adult fertility, that he initiated for my doctorate under J.-C. Beauvillain at the University of Lille, France. These studies have led and continue to lead to many seminal contributions and groundbreaking concepts in our understanding of the central control of mammalian reproduction. Following my postdoctoral training, Dr. Prevot returned to France to take up a tenured Associate Researcher position at the Inserm in 2002, establishing an independent research group at Lille. In 2004, he became head of the “Development and Plasticity of the Postnatal Brain” Inserm laboratory at Lille, which currently comprises 22 researchers, clinicians, postdoctoral fellows, Ph.D. students and technicians. Dr. Prevot was officially promoted to the rank of Research Director in 2009. His current research focuses on Systems Neuroscience and Neuroendocrinology, in particular the brain circuits that control reproduction and metabolism and the neural pathways through which they respond to peripheral information.
1. Bellefontaine N, Chachlaki K, Parkash J, Vanaker C, Colledge W, d’Anglemont de Tassigny X, Garthwaite J, Bouret SG, Prevot V. Leptin facilitates reproduction through neuronal nitric oxide signaling in the hypothalamic preoptic region. J Clin Invest 124:2550-2559, 2014.
In this study, we established that neurons synthesizing nitric oxide (NO) in the preoptic region of the hypothalamus constitute a key neuronal population for the permissive actions of leptin in the onset of puberty and adult fertility. We showed that leptin coordinates fertility by inducing the synthesis of the freely-diffusible volume transmitter NO, through the activation of neuronal NO synthase (nNOS) in these neurons.
2. Giacobini P, Parkash J, Campagne C, Messina A, Casoni F, Vanacker C, Langlet F, Hobo B, Cagnoni G, Gallet S, Hanchate NK, Mazur D, Taniguchi M, Mazzone M, Verhaagen J, Ciofi P, Bouret SG, Tamagnone L, Prevot V. Brain Endothelial Cells Control Fertility through Ovarian-Steroid-Dependent Release of Semaphorin 3A. PLoS Biology 12(3):e1001808, 2014.
This study showed that endothelial-cell-derived Sema3A is an outgrowth-promoting factor that regulates axonal plasticity and neurohormone release in the adult brain in response to the ovarian cycle. These findings establish a previously unknown mechanism of axonal plasticity in the adult brain involving vascular Sema3A, and have broad implications for endothelial-cell-to-neuron communication as a general mediator of axonal plasticity in the mature nervous system.
3. Balland E, Dam J, Langlet F, Caron E, Steculorum S, Messina A, Rasika S, Falluel-Morel A, Anouar Y, Dehouck B, Trinquet E, Jockers R, Bouret SG, Prevot V. Hypothalamic tanycytes are an ERK-gated conduit for leptin into the brain. Cell Metab 19, 293-301, 2014. (also Cell Metab Previews 173-175).
In this study, we established that tanycytes, specialized hypothalamic glia lining the floor of the third ventricle, are involved in regulating energy homeostasis in the central nervous system by controlling leptin access to the hypothalamus in a leptin-receptor- and ERK-pathway-dependent manner. These findings, which shed new light on the mechanisms underlying central leptin resistance, hold therapeutic potential for treating obesity.
4. Prevot V. Puberty in mice and rats. In: Knobil and Neill’s Physiology of Reproduction, Fourth Edition Edition (Plant TM, Zeleznik J, eds). New York: Elsevier, pp in press, 2014.
5. Langlet F, Levin BE, Luquet S, Mazzone M, Messina A, Dunn-Meynell AA, Balland E, Lacombe A, Mazur D, Carmeliet P, Bouret SG, Prevot V*, Dehouck B. Tanycytic VEGF-A Boosts Blood-Hypothalamus Barrier Plasticity and Access of Metabolic Signals to the Arcuate Nucleus in Response to Fasting. Cell Metab 17:607-617, 2013. (also Cell Metab Previews 467-468) * Corresponding author.
In this work, our data unveil a new physiological concept in the maintenance of energy homeostasis, in which blood glucose levels, by regulating tanycytic VEGF-A expression, modulate the organization of their tight junctions as well as the permeability of median eminence capillary loops in the ventromedial arcuate nucleus of the hypothalamus, and thereby control the access of circulating homeostatic signals to brain circuits that regulate metabolism.
Ongoing Research Support
- FRM (French Medical Research Foundation). “Equipe FRM DEQ20130326524” Coordinator and PI: Vincent Prevot. 2013-2015.
- ANR (French National Research Agency) Blanche PERIPULSE (Coordinator Patrice Mollard, Inserm Montpellier). PI: Vincent Prevot.for the Prevot research team, 2013-2015.
- SERVIER Pharmaceutical Industries Research Contract. PI: Vincent Prevot. 2012-2014.
Election to Executive Committees and Advisory Boards
- 2015-present: Treasurer of the Federation of European Neuroscience Societies (FENS).
- 2014- present: Member of the Scientific Council of the French Medical Research Foundation (FRM).
- 2013-present: President of the French Society for Neuroendocrinology
- 2012-present: Member of the Executive Committee of the Federation of European Neuroscience Societies (FENS).
- 2012-present: Member of the Council of the International Neuroendocrinology Federation
- 2012-present: Member of the board of the French Glial Cell Club.
- 2008-2009: Treasurer of the French Society for Neuroscience.
- 2009-2011: Treasurer of the French Society for Neuroendocrinology.
- 2006-2011: Member of the board of the French Society for Neuroendocrinology.
- 2006-2009: Member of the board of the French Society for Neuroscience.
- 2014-: Editorial board of Endocrinology (IF: 4.7).
- 2011-present: Editorial board of the Journal of Neuroendocrinology (IF: 3.1).
- 2008-present: Contributing Editor of the European Journal of Neuroscience (EJN) (IF: 3.6).
- 2010: Invited editor of the EJN special issue on “Plasticity of Neuroendocrine systems” Volume 32, number 12.