6875 Boulevard Lasalle
Professor of Psychiatry, Department of Medicine, McGill University
Canada Research Chair for the Neurobiology of Mental Disorders
Graham Boeckh Chair for Schizophrenia Research
Research Director at CNRS
Pathophysiology of Psychiatric Disorders
Our research group is genuinely interested in the Pathophysiology of Psychiatric Disorders, investigating the molecular and cellular processes that are involved in the appearance of the main symptoms of these disorders. We are more precisely focusing on two devastating disorders, Schizophrenia and Major Depression, which respectively account worldwide for 1.5% and 20% of the people in the general population. To reach our objectives, we combined molecular, biochemical, electrophysiological and behavioral approaches. For these studies, we are generating original animal models with genetic engineering, and we used “state of the art” techniques, as optogenetic stimulations in the awake animal or miRNA transcriptomic analysis for example.
• For schizophrenia, we are presently unraveling unsuspected effects of dopamine in the frontal cortex and the hippocampus, and starting to understand precisely, at the cellular and network levels, how they are put into play.
• For depression, our fundamental and preclinical projects are investigating mechanisms contributing to individual vulnerability or resistance (resiliency) to stress and the etiology of depression.
The combination of our approaches will not only enriches our hypotheses, but will also offers a strong potential to recognize common mechanisms occurring in these two major psychiatric disorders. All our studies aim, at the mid-term, to be translated into experimental medicine protocols in collaboration with psychiatrists.
Rocchetti et al., Presynaptic D2 Dopamine Receptors Control Long-Term Depression Expression and Memory Processes in the Temporal Hippocampus. 2015, Biol. Psychiatry, 77, 513-525.
Couroussé et al., Brain Organic Cation Transporter-2 controls response and vulnerability to stress and GSK3ß signaling.. 2014, Mol Psychiatry, in press.
DeGois S. et al., Ctr9, a protein of the transcription complex Paf1, regulates the Dopamine Transporter activity at the plasma membrane. J. Biol. Chem., in press.
Giros B., C. Gros, B. Solhonne & J.C. Schwartz. Characterization of aminopeptidases responsible for inactivating endogenous enkephalin in brain slices using peptidase inhibitors and antiaminopeptidase M antibodies. Molec. Pharmacol., 1986, 29, 281-287.
Giros B., P. Sokoloff, M.P. Martres, J.F. Riou, J.L. Emorine & J.-C. Schwartz. Alternative splicing directs the expression of two D-2 dopamine receptor isoforms. Nature, 1989, 342, 923-926.
Sokoloff P., B. Giros, M.P. Martres, M.L.Bouthenet & J.C. Schwartz. Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature, 1990, 347,146-151.
Bouthenet M.L., E. Souil, M.P. Martres, P. Sokoloff, B. Giros & J.C. Schwartz. Localization of dopamine D3 receptor RNA in the rat brain using in situ hybridization histochemistry: comparison with dopamine D2 receptor mRNA. Brain Res., 1991, 564, 203-219.
Piomelli, D., C. Pilon, B. Giros, P. Sokoloff, M.P. Martres & J.C. Schwartz. Dopamine activation of the arachidonic acid cascade via a modulatory mechanism as a basis for D1/D2 receptor synergism. Nature, 1991, 353, 164-167.
Giros B., S. El Mestikawy, L. Bertrand & M. G. Caron. Cloning and functionnal characterization of a cocaine sensitive dopamine transporter. 1991, FEBS Letters, 295, 149-154.
Giros B. , S. El Mestikawy, N. Godinot, K. Zheng, H. Han, T. Yang-Feng & M.G. Caron. Cloning, pharmacological characterization and chromosome assignment of the human dopamine transporter. Mol. Pharmacol., 1992, 42, 383-390.
Giros B. & M.G. Caron. Molecular characterization of the dopamine transporter. Trends Pharmacol. Sci., 1993, 14, 43-49.
Kim K.-M, S.F. Kingsmore, H. Han, T. L. Yang.Feng, N. Godinot, M.F. Seldin, M.G. Caron & B. Giros. Cloning of the human glycine transporter Type1: molecular and pharmacological characterization of novel isoform variants and chromosomal localization of the gene in the human and mouse genome. Mol. Pharmacol., 1994, 45, 608-617.
Giros B., M. Jaber, S.R. Jones, R.M. Wightman & M.G. Caron. Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. 1996, Nature, 379, 606-612.
Jaber M., W.J. Koch, H. Rockman, B. Smith, R.A. Bond, K.K. Sulik, J. Ross Jr., R.J. Lefkowitz, M.G. Caron & B. Giros. Essential role of ?-Adrenergic Receptor Kinase-1 in cardiac development and function. 1996, Proc. Natl. Acad. Sci. USA, 93, 12974-12979.
Spielewoy, C., F. Gonon, C. Roubert, V. Fauchey, M. Jaber, M. Caron, B. Roques, M. Hamon, C. Betancur, R. Maldonado & B. Giros. Increased rewarding properties of morphine in dopamine-transporter knockout mice. 2000, Eur. J. Neurosci., 12, 1827-1837.
Roubert, C., Cox, P.J., Bruss, M., Hamon, M., Bonisch, H. & Giros, B. Determination of Residues in the Norepinephrine Transporter that are Critical for Tricyclic Antidepressant Affinity. 2001, J Biol Chem., 276: 8254-8260.
Sagné C., Agulhon C., Ravassard P., Darmon M., Hamon M., El Mestikawy S., Gasnier B. & Giros B. Identification and characterisation of a lysosomal transporter for small neutral amino acids. 2001, Proc. Natl. Acad. Sci. USA, 98 :7206-7211.
Gras C., Herzog E., Bellenchi G.C., Bernard V., Ravassard P., Pohl M., Gasnier B., Giros B. & S. El Mestikawy. A third vesicular glutamate transporter expressed by cholinergic and serotoninergic neurons. 2002, J. Neurosci., 22, 5442-5451.
Jamain S, Quach H, Betancur C, Rastam M, Colineaux C, Gillberg Ic, Soderstrom H, Giros B, Leboyer M, Gillberg C, & Bourgeron T; Paris Autism Research International Sibpair Study.. Mutations of the X-linked neuroligins HNL3 and HNL4X are associated with autism. 2003, Nature genetics, 34, 27-29.
Agulhon C, Rostaing P, Ravassard P, Sagne C, Triller A & Giros B. The lysosomal amino acid transporter LYAAT-1 in the rat central nervous system: an in situ hybridization and immunohistochemical study. 2003 J. Comp. Neurol. 462, 71-89.
Vialou V, Amphoux A, Zwart R, Giros B, & Gautron S Organic cation transporter 3 (Slc22a3) is implicated in salt-intake regulation. J Neurosci. 2004 24, 2846-2851.
Tzavara ET, Li DL, Moutsimilli L, Bisogno T, Marzo VD, Phebus LA, Nomikos GG, Giros B. Endocannabinoids Activate Transient Receptor Potential Vanilloid 1 Receptors to Reduce Hyperdopaminergia-Related Hyperactivity: Therapeutic Implications. Biological Psychiatry, 2006, 59, 508-515.
Vinatier J., Herzog E., Plamont M.A., Wojcik S., Schmidt A., Brose N., Daviet L., El Mestikawy S., Giros B. Interaction between the vesicular glutamate transporter type 1 and endophilin A1, a protein essential for endocytosis. 2006, J. Neurochem 97, 1111-1125.
Bacq A, Balasse L, Biala G, Guiard B, Gardier A, Schinkel A, Louis F, Vialou V, Martres MP, Hamon M, Giros B, Gautron S. Organic cation transporter 2 controls norepinephrine and serotonin clearance in the brain and can modulate the neurochemical and behavioral responses to antidepressants. Molecular Psychiatry, 2012, 17, 926-939.
Farley S, Dumas S, El Mestikawy S, Giros B. Increased expression of the Vesicular Glutamate Transporter-1 (VGLUT1) in the prefrontal cortex correlates with differential vulnerability to chronic stress in various mouse strains: Effects of fluoxetine and MK-801. Neuropharmacology, 2012, 62, 503-517.
Manitt C, Eng C, Pokinko M, Ryan RT, Torres Berrío A, Grant A, Yogendran SV, Daubaras MJJ, Schmidt ERE, Krimpenfort P, Cooper HM, Pasterkamp RJ, Kolb B, Wong TP, Nestler EJ, Giros B, Flores C. The netrin receptor DCC (Deleted in Colorectal Cancer) is an adolescence-specific guide for the maturation of mesocortical dopamine functions. 2013 Tranlational Psychiatry, 17, e338
Blum ID, Zhu L, Moquin L, Kokoeva M, Gratton A, Giros B, Storch KF. A highly-tunable dopaminergic oscillator generates ultradian rhythms of behavioral arousal. Elife. 2014 Dec 29;3. doi: 10.7554/eLife.05105.
Rocchetti J, Isingrini E, Dal Bo G, Sagheby S, Tronche F, Moquin L, Gratton A, Levesque D, Wong TP, Rubinstein M, Giros B. Presynaptic D2 Dopamine Receptors Control Long-Term Depression Expression and Memory Processes in the Temporal Hippocampus. Biological Psychiatry, 2015, 77, 513-525.
Couroussé T, Bacq A, Belzung C, Guiard B, Balasse L, Louis F, Le Guisquet A-M, Gardier AM, Schinkel AH, Giros B, Gautron S. Brain Organic Cation Transporter-2 controls response and vulnerability to stress and GSK3ß signaling. Molecular Psychiatry, 2015, in press.
DeGois S, Slama P, Pietrancosta N, Bouvrais-Veret C, Louis F, Daviet L, Giros B. Ctr9, a protein of the transcription complex Paf1, regulates the Dopamine Transporter activity at the plasma membrane. J. Biol. Chem., 2015, in press.
|1983-1984||U-109 INSERM, Paris, France||Jean-Charles Schwartz|
|1984||Lab. Neuro. Exp., Rouen, France||Jean Costentin|
|1984-1987||U-109 INSERM, Paris, France||Jean-Charles Schwartz|
|1987||Genentech, San Francisco, USA||Bernard Malfroy|
|1988-1991||U-109 INSERM, Paris, France||Jean-Charles Schwartz|
|1991-1994||HHMI, Duke Univ., Durham, USA||Marc G. Caron|
|1994-1998||U-288 INSERM, Paris, France||Michel Hamon|
|1999-2008||U-513 INSERM, Créteil, France||Bruno Giros|
|2009-2013||CNRS UMR7224 INSERM 952||Bruno Giros|
|2008-||Douglas Hospital Research Center||Bruno Giros|
Bruno Giros authored over 170 publications (Hf=52), has been recognized by the Institute for Scientific Information as a “Most Highly Cited Scientist” in the area of pharmacology, and has received numerous awards, including the very prestigious “Médaille d’Argent” from the CNRS.
In the news
Deleting IGF-1 receptor from forebrain neurons confers neuroprotection during stroke and upregulates endocrine somatotropin. J Cereb Blood Flow Metab. 2017;37(2):396-412.
Selective genetic disruption of dopaminergic, serotonergic and noradrenergic neurotransmission: insights into motor, emotional and addictive behaviour. J Psychiatry Neurosci. 2016;41(3):169-81.
Resilience to chronic stress is mediated by noradrenergic regulation of dopamine neurons. Nat Neurosci. 2016;19(4):560-3.
Highly delayed systemic translocation of aluminum-based adjuvant in CD1 mice following intramuscular injections. J Inorg Biochem. 2015;152:199-205.
The absence of VGLUT3 predisposes to cocaine abuse by increasing dopamine and glutamate signaling in the nucleus accumbens. Mol Psychiatry. 2015;20(11):1448-59.
GABAB receptor cell-surface export is controlled by an endoplasmic reticulum gatekeeper. Mol Psychiatry. 2015.
Ctr9, a Protein in the Transcription Complex Paf1, Regulates Dopamine Transporter Activity at the Plasma Membrane. J Biol Chem. 2015;290(29):17848-62.
Brain organic cation transporter 2 controls response and vulnerability to stress and GSK3β signaling. Mol Psychiatry. 2015;20(7):889-900.
Presynaptic D2 dopamine receptors control long-term depression expression and memory processes in the temporal hippocampus. Biol Psychiatry. 2015;77(6):513-25.
Morphometric characterization of microglial phenotypes in human cerebral cortex. J Neuroinflammation. 2014;11:12.
dcc orchestrates the development of the prefrontal cortex during adolescence and is altered in psychiatric patients. Transl Psychiatry. 2013;3:e338.