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SBRI is in "Le Monde"

Published on January 31, 2012


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Vincent Leviel

Position: Director of Research

Company: Inserm u846


Mailing Address:
18 avenue du Doyen Jean Lépine

69675 - Bron Cedex - France
External Link: www.sbri.fr
E-mail: Vincent.Leviel@inserm.fr
Phone: 04.72.91.34.45
Fax: 04.72.91.34.61


Group(s):
Cell replacement therapy for early Parkinson’s disease - Transversal projects
Neurobiology of executive functions - Teams

Research interest

The objectives concern the detection of chemical alterations in the brain and behavioral deficits during early phases of progressive dopaminergic lesion simulating Parkinson’s disease. This in view to ameliorate the diagnostic ability, and to propose new therapeutic processes. This is based on longitudinal approaches using experimental models with 6-OHDA and MPTP, toxic substances of the dopaminergic central neurons.
First, Parkinson’s disease etiology is approached. We investigate the relationship between striatal dopamine loss (the presumed basis of parkinsonian symptoms) and striatal dopamine metabolism. Paradoxically, we observed that dopamine release in the striatum is initialy increased in response to partial depopulation of the nigral dopamine cells as it was also observed during the early phases of Parkinson’s disease. We hypothesize that a glutamate-mediated upregulation of the striatal dopamine release delays the appearance of the symptoms, but also has deleterious consequences due to dopamine neurotoxicity.
Second, discovery of new treatments for Parkinson’s disease (PD) is impeded by an incomplete understanding of the relationship between the pathology of the disease and its symptoms. Thus we analyze the relationship between dopamine (DA) dysfunction and parkinsonism by comparing the symptoms and neurophysiologic abnormalities induced by transient blockade or permanent lesion of DA innervation in the motor striatum of behaving monkeys. We analyze the longitudinal electrophysiological follow-up of cognitive event-related potentials (feedback-related potentials) and of global oscillatory patterns that are associated to cortical dopaminergic-dependant processes and to thalamo-cortical interactions, respectively. The objective is based on chronic EEG technology in monkeys trained to cognitive tasks. The major milestone will be the characterization of neurobiological markers of early Parkinson’s symptoms. We also evaluate the dynamic, interdependence of changes in striatal and cortical dopaminergic transmission during progressive mesencephalic dopaminergic lesion. The objective is based on chronic microdialysis and voltametry, and on periodic PET examinations. The major milestone will be to establish the precise timetable of fluctuations in dopaminergic transmission in target structures.
Publications
Vezoli J, Fifel K, Leviel V, Dehay C, Kennedy H, Cooper HM, Gronfier C, Procyk E (2011) Early Presymptomatic and Long-Term Changes of Rest Activity Cycles and Cognitive Behavior in a MPTP-Monkey Model of Parkinson’s Disease. PLoS ONE 6(8): e23952 download
Dzahini K, Dentresangle C, Le Cavorsin M, Bertrand A, Detraz I, Savasta M, Leviel V (2010) Pre-synaptic glutamate-induced activation of DA release in the striatum after partial nigral lesion J Neurochem 113(6): 1459-1470 download
Wianny F, Bernat A, Huissoud C, Marcy G, Markossian S, Cortay V, Giroud P, Leviel V, Kennedy H, Savatier P, Dehay C (2008) Derivation and cloning of a Novel Rhesus ES cell line stably expressing Tau-GFP Stem Cells 26(6):1444-53 download
Hassoun W, Thobois S, Ginovart N, Garcia-Larrea L, Cavorsin ML, Guillouet S, Bonnefoi F, Costes N, Lavenne F, Martin JP, Broussolle E, Leviel V. (2005) Striatal dopamine during sensorial stimulations: a [18F]FDOPA PET study in human and cats. Neurosci Lett. 383(1-2):63-7. Epub 2005 Apr 21 download
Thobois S, Hassoun W, Ginovart N, Garcia-Larrea L, Le Cavorsin M, Guillouet S, Bonnefoi F, Costes N, Lavenne F, Broussolle E, Leviel V. (2004) Effect of sensory stimulus on striatal dopamine release in humans and cats: a [(11)C]raclopride PET study. Neurosci Lett. 368(1):46-51 download
Hassoun W, Le Cavorsin M, Ginovart N, Zimmer L, Gualda V, Bonnefoi F, Leviel V. (2003) PET study of the [11C]raclopride binding in the striatum of the awake cat: effects of anaesthetics and role of cerebral blood flow. Eur J Nucl Med Mol Imaging. 30(1):141-8. Epub 2002 Sep 17 download
Rbah L, Leviel V, Zimmer L. (2003) Displacement of the PET ligand 18F-MPPF by the electrically evoked serotonin release in the rat hippocampus. Synapse. 49(4):239-45 download
Romestaing C, Denoroy L, Parrot S, Martin V, Leviel V, Vega C, Massarelli R. (2003) Glutamate agonists release excitatory aminoacids from rat astrocytes. Arch Ital Biol. 141(1):11-8
Ginovart N, Hassoun W, Le Cavorsin M, Veyre L, Le Bars D, Leviel V. (2002) Effects of amphetamine and evoked dopamine release on [11C]raclopride binding in anesthetized cats. Neuropsychopharmacology.27(1):72-84 download
Zimmer L, Hassoun W, Pain F, Bonnefoi F, Lanièce P, Mastrippolito R, Pinot L, Pujol JF, Leviel V. (2002) SIC, an intracerebral beta(+)-range-sensitive probe for radiopharmacology investigations in small laboratory animals: binding studies with (11)C-raclopride. J Nucl Med. 43(2):227-33 download
Leviel V (2001) The reverse transport of DA, what physiological significance? Neurochem Int 38(2):83-106 download
Dentresangle C, Le Cavorsin M, Savasta M, Leviel V. (2001) Increased extracellular DA and normal evoked DA release in the rat striatum after a partial lesion of the substantia nigra. Brain Res.893(1-2):178-85 download
Ginovart N, Hassoun W, Le Bars D, Weissmann D, Leviel V. (2000) In vivo characterization of p-[(18)F]MPPF, a fluoro analog of WAY-100635 for visualization of 5-HT(1a) receptors. Synapse. 35(3):192-200 download
Laschet J, Trottier S, Leviel V, Guibert B, Bansard JY, Chauvel P, Bureau M. (1999) Heterogeneous distribution of polyamines in temporal lobe epilepsy. Epilepsy Res. 35(2):161-72 download
Moresco RM, Loc'h C, Ottaviani M, Guibert B, Leviel V, Maziere M, Fazio F, Maziere B. (1999) Effects of dopamine on the in vivo binding of dopamine D2 receptor radioligands in rat striatum. Nucl Med Biol. 26(1):91-8 download
Olivier V, Gobert A, Guibert B, Leviel V. (1999) The in vivo modulation of dopamine synthesis by calcium ions: influences on the calcium independent release. Neurochem Int.35(6):431-8 download
Frain O, Leviel V. (1998) Mesencephalic THmRNA-reduced expression by blocking axonal transport with colchicine. Neuroreport. 9(7):1529-32 download
Le Bars D, Lemaire C, Ginovart N, Plenevaux A, Aerts J, Brihaye C, Hassoun W, Leviel V, Mekhsian P, Weissmann D, Pujol JF, Luxen A, Comar D. (1998) High-yield radiosynthesis and preliminary in vivo evaluation of p-[18F]MPPF, a fluoro analog of WAY-100635. Nucl Med Biol. 25(4):343-50 download
Pasqualini C, Olivier V, Guibert B, Frain O, Leviel V. (1996) Rapid stimulation of striatal dopamine synthesis by estradiol. Cell Mol Neurobiol. 16(3):411-5 download
Vankova M, Boyer PA, Leviel V, Arluison M (1996) Opposite changes in the expression of enkephalin in the amygdala and hypothalamus after lesions of the bed nucleus of the stria terminalis in the rat. Neuroscience. 74(1):219-35 download
Olivier V, Guibert B, Leviel V. (1995) Direct in vivo comparison of two mechanisms releasing dopamine in the rat striatum. Brain Res. 695(1):1-9 download
Pasqualini C, Olivier V, Guibert B, Frain O, Leviel V. (1995) Acute stimulatory effect of estradiol on striatal dopamine synthesis. J Neurochem 65(4):1651-7 download
Arluison M, Brochier G, Vankova M, Leviel V, Villalobos J, Tramu G. (1994) Demonstration of peptidergic afferents to the bed nucleus of the stria terminalis using local injections of colchicine. A combined immunohistochemical and retrograde tracing study. Brain Res Bull. 34(4):319-37
Boyer PA, Trembleau A, Leviel V, Arluison M. (1994) Effects of intranigral injections of colchicine on the expression of some neuropeptides in the rat forebrain: an immunohistochemical and in situ hybridization study. Brain Res Bull. 33(5):541-60
Hantraye P, Guibert B, Biguet NF, Lavergne A, Leviel V. (1994) TH mRNA over-expression in rats with chronic excitotoxic striatal lesions. Neuroreport. 5(18):2621-4
Lavergne A, Frain O, Guibert B, Biguet NF, Leviel V. (1994) Regulation of tyrosine hydroxylase gene expression in mesencephalic dopamine neurons: effect of imipramine treatment. Neurosci Lett. 182(2):167-71
Pasqualini C, Guibert B, Frain O, Leviel V. (1994) Evidence for protein kinase C involvement in the short-term activation by prolactin of tyrosine hydroxylase in tuberoinfundibular dopaminergic neurons. J Neurochem. 62(3):967-77 download
Pasqualini C, Guibert B, Leviel V. (1993) Short-term inhibitory effect of estradiol on tyrosine hydroxylase activity in tuberoinfundibular dopaminergic neurons in vitro. J Neurochem. 60(5):1707-13 download
Gobert A, Guibert B, Lenoir V, Kerdelhue B, Leviel V. (1992) GnRH-associated peptide (GAP) is present in the rat striatum and affects the synthesis and release of dopamine. J Neurosci Res. 31(2):359-64
Laschet J, Trottier S, Grisar T, Leviel V. (1992) Polyamine metabolism in epileptic cortex. Epilepsy Res.12(2):151-6
Sara SJ, Dyon-Laurent C, Guibert B, Leviel V. (1992) Noradrenergic hyperactivity after partial fornix section: role in cholinergic dependent memory performance. Exp Brain Res 89(1):125-32
Vankova M, Arluison M, Leviel V, Tramu G. (1992) Afferent connections of the rat substantia nigra pars lateralis with special reference to peptide-containing neurons of the amygdalo-nigral pathway. J Chem Neuroanat. 5(1):39-50
Leviel V, Guibert B, Mallet J, Faucon-Biguet N. (1991) Induction of tyrosine hydroxylase in the rat substantia nigra by local injection of forskolin. J Neurosci Res. 30(2):427-32
Varrault A, Leviel V, Bockaert J (1991) 5-HT1A-sensitive adenylyl cyclase of rodent hippocampal neurons: effects of antidepressant treatments and chronic stimulation with agonists. J Pharmacol Exp Ther. 257(1):433-8 download
Arluison M, Vankova M, Cesselin F, Leviel V. (1990) Origin of some enkephalin-containing afferents to the ventro-medial region of the globus pallidus in the rat. Brain Res Bull. 25(1):25-34.
Leviel V, Fayada C, Guibert B, Chaminade M, Machek G, Mallet J, Biguet NF. (1990) Short- and long-term alterations of gene expression in limbic structures by repeated electroconvulsive-induced seizures. J Neurochem. 54(3):899-904 download
Leviel V, Gobert A, Guibert B. (1990) The glutamate-mediated release of dopamine in the rat striatum: further characterization of the dual excitatory-inhibitory function. Neuroscience. 39(2):305-12
Horellou P, Guibert B, Leviel V, Mallet J. (1989) Retroviral transfer of a human tyrosine hydroxylase cDNA in various cell lines: regulated release of dopamine in mouse anterior pituitary AtT-20 cells. Proc Natl Acad Sci U S A. 86(18):7233-7
Leviel V, Gobert A, Guibert B. (1989) Direct observation of dopamine compartmentation in striatal nerve terminal by 'in vivo' measurement of the specific activity of released dopamine. Brain Res.499(2):205-13
Darmon MC, Guibert B, Leviel V, Ehret M, Maitre M, Mallet J. (1988) Sequence of two mRNAs encoding active rat tryptophan hydroxylase. J Neurochem. 51(1):312-6 download
Horellou P, Le Bourdellès B, Clot-Humbert J, Guibert B, Leviel V, Mallet J. (1988) Multiple human tyrosine hydroxylase enzymes, generated through alternative splicing, have different specific activities in Xenopus oocytes. J Neurochem.51(2):652-5 download
Kalcheim C, Leviel V. (1988) Stimulation of collagen production in vitro by ascorbic acid released from explants of migrating avian neural crest. Cell Differ. 22(2):107-14
Pasqualini C, Bojda F, Gaudoux F, Guibert B, Leviel V, Teissier E, Rips R, Kerdelhue B. (1988) Changes in tuberoinfundibular dopaminergic neuron activity during the rat estrous cycle in relation to the prolactin surge: alteration by a mammary carcinogen. Neuroendocrinology. 48(3):320-7
Fayada C, Guibert B, Patey G, Cupo A, Chaminade M, Rossier J, Leviel V. (1987) Release of [Met]enkephalin in the central nucleus of the amygdala is increased by application of potassium in the substantia nigra. Neuropeptides. 9(1):9-17
Leviel V, Guibert B. (1987) Involvement of intraterminal dopamine compartments in the amine release in the cat striatum. Neurosci Lett. 76(2):197-202
Romo R, Gaudry-Talarmain YM, Chéramy A, Godeheu G, Leviel V, Chesselet MF, Glowinski J, Israël M. (1987) Different effects of electrical stimulation of the mesencephalic and pontine reticular formation on the release of dopamine and acetylcholine in the cat caudate nucleus. Neurosci Lett. 78(1):57-62
Horellou P, Guibert B, Leviel V, Mallet J. (1986) A single RNA species injected in Xenopus oocyte directs the synthesis of active tyrosine hydroxylase. FEBS Lett. 205(1):6-10 download
Leviel V, Charriere B, Fayada C, Guibert B. (1986) Nigroamygdaloid dopamine neurons: nigral modulation of their activity. Brain Res. 381(2):205-14
Mintz I, Hammond C, Guibert B, Leviel V. (1986) Stimulation of the subthalamic nucleus enhances the release of dopamine in the rat substantia nigra. Brain Res. 376(2):406-8
Charton G, Rovira C, Ben-Ari Y, Leviel V. (1985) Spontaneous and evoked release of endogenous Zn2+ in the hippocampal mossy fiber zone of the rat in situ. Exp Brain Res. 58(1):202-5
Leviel V, Kerny C, Barberis C, Guibert B, Daudet F. (1984) Blockade by frontocortical lesion of reciprocal regulation between the two nigrostriatal dopaminergic pathways. Neuroscience.13(1):53-9
Sara SJ, Grecksch G, Leviel V. (1984) Intracerebroventricular apomorphine alleviates spontaneous forgetting and increases cortical noradrenaline. Behav Brain Res 13(1):43-52
Barberis C, Daudet F, Charriere B, Guibert B, Leviel V. (1983) Release of adenosine in vivo from cat caudate nucleus. Neurosci Lett. 41(1-2):179-82
Charriere B, Daudet F, Guibert B, Barberis C, Leviel V. (1983) In situ release of dopamine in the nucleus amygdaloideus centralis. Brain Res. 271(2):386-7
Chéramy A, Chesselet MF, Romo R, Leviel V, Glowinski J. (1983) Effects of unilateral electrical stimulation of various thalamic nuclei on the release of dopamine from dendrites and nerve terminals of neurons of the two nigrostriatal dopaminergic pathways. Neuroscience.8(4):767-80
Daudet F, Leviel V, Kerny C, Guibert B, Barberis C. (1983) Effects of naloxone on dopamine release in the nigrostriatal system. Eur J Pharmacol. 95(3-4):199-205
Cheramy A, Leviel V, Glowinski J. (1981) Dendritic release of dopamine in the substantia nigra. Nature. 289(5798):537-42 download
Leviel V, Chesselet MF, Glowinski J, Chéramy A. (1981) Involvement of the thalamus in the asymmetric effects of unilateral sensory stimuli on the two nigrostriatal dopaminergic pathways in the cat. Brain Res. 2;223(2):257-72
Greenfield S, Cheramy A, Leviel V, Glowinski J. (1980) In vivo release of acetylcholinesterase in cat substantia nigra and caudate nucleus. Nature. 284(5754):355-7 download
Champagnat J, Denavit-Saubié M, Henry JL, Leviel V. (1979) Catecholaminergic depressant effects on bulbar respiratory mechanisms. Brain Res.160(1):57-68
Leviel V, Chéramy A, Nieoullon A, Glowinski J. (1979) Symmetric bilateral changes in dopamine release from the caudate nuclei of the cat induced by unilateral nigral application of glycine and GABA-related compounds. Brain Res. 175(2):259-70
Leviel V, Chéramy A, Glowinski J. (1979) Role of the dendritic release of dopamine in the reciprocal control of the two nigro-striatal dopaminergic pathways. Nature. 280(5719):236-9 download
Michelot R, Leviel V, Giorguieff-Chesselet MF, Chéramy A, Glowinski J. (1979) Effects of the unilateral nigral modulation of substance P transmission on the activity of the two nigro-striatal dopaminergic pathways. Life Sci. 24(8):715-23
Michelot R, Leviel V, Torrens Y, Glowinski J, Chéramy A. (1979) In vivo release of substance P in the cat substantia nigra. Neurosci Lett. 15(2-3):141-6
Nieoullon A, Cheramy A, Leviel V, Glowinski J. (1979) Effects of the unilateral nigral application of dopaminergic drugs on the in vivo release of dopamine in the two caudate nuclei of the cat. Eur J Pharmacol. 53(3):289-96
Brotchi J, Tanaka T, Leviel V. (1978) Lack of activated astrocytes in the kindling phenomenon. Exp Neurol. ;58(1):119-25
Cheramy A, Michelot R, Leviel V, Nieoullon A, Glowinski J, Kerdelhue B. (1978) Effect of the immunoneutralization of substance P in the cat substantia nigra on the release of dopamine from dendrites and terminals of dopaminergic neurons. Brain Res. 155(2):404-8
Leviel V, Naquet R. (1977) A study of the action of valproic acid on the kindling effect. Epilepsia. 18(2):229-34
Leviel V, Beillevaire T, Naquet R. (1977) Preliminary study of the comparative action of 1 methyl-2 (2 naphtyl) aziridine on kindling effect and on paradoxical sleep (author's transl) Rev Electroencephalogr Neurophysiol Clin.7(2):225-31



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