Bruno Giros PhD
6875 Boulevard LaSalle
Canada Research Chair for the Neurobiology of Mental Disorders - Tier 1
Graham Boeckh Chair for Schizophrenia Research
Researcher, Douglas Research Centre
Full Professor, Department of Psychiatry, McGill University
Research Director, French National Centre for Scientific Research (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.
Top publications (1989-2018)
from a total of > 180 publications in peer-reviewed journals
(Web of Science : 18,000 citations; Hf=58 – Google scholar : 24,000 citations ; Hf=69)
- Giros B, Sokoloff P, Martres MP, Riou JF, Emorine JL & Schwartz JC. Alternative splicing directs the expression of two D-2 dopamine receptor isoforms. Nature, 1989, 342, 923-926.
- Sokoloff P, Giros B, Martres MP, Bouthenet ML & Schwartz JC. Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature, 1990, 347,146-151.
- Giros B, Jaber M, Jones SR, Wightman RM & Caron MG. Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature, 1996, 379, 606-612.
- Jaber M, Koch WJ, Rockman H, Smith B, Bond RA, Sulik KK, Ross Jr. J, Lefkowitz RJ, Caron MG & Giros B. Essential role of b-Adrenergic Receptor Kinase-1 in cardiac development and function. Proc. Natl. Acad. Sci. USA, 1996, 93, 12974-12979.
- 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. Proc. Natl. Acad. Sci. USA, 2001, 98 :7206-7211.
- 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.
- 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. Neuropharmacol., 2012, 62, 503-517.
- 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, 290, 17848-17862.
- 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.
- Isingrini E, Perret L, Rainer Q, Amilhon B, Guma E, Tanti A, Martin G, Robinson J, Moquin L, Marti F, Mechawar N, Williams S, Gratton A & Giros B. Resilience against chronic stress is mediated by noradrenergic regulation of dopamine neurons. Nature Neurosci, 2016, 19, 560-563.
- Isingrini E, Guinaudie C, Perret LC, Rainer Q, Moquin L, Gratton A, Giros B. Genetic elimination of dopamine vesicular stocks in the nigrostriatal pathway replicates Parkinson’s disease motor symptoms without neuronal degeneration in adult mice. Scientific Reports, 2017, 7, 12432.
- Erdozain AM, De Gois S, Bernard V, Gorgievski V, Pietrancosta N, Dumas S, Macedo CE, Vanhoutte P, Ortega JE, Meana JJ, Tzavara ET, Vialou V, Giros B. Structural and functional characterization of the interaction of snapin with the Dopamine Transporter: differential modulation of psychostimulant actions. Neuropsychopharmacol., 2018, 43, 1041-1051.
- Apazoglou K, Farley S, Gorgievski V, Belzeaux R, Lopez JP., Grenier J, Ibrahim E, El Khoury M-A, Tse Y.C., Mongredien R, Barbé A, Antunes de Macedo CE, Jaworski W, Bochereau A, Orrico A, Isingrini E, Guinaudie C, Mikasova L, Louis F, Gautron S, Groc L, Massaad C, Yildirim F, Vialou V, Dumas S, Marti F, Mechawar N, Morice E, Wong TP, Caboche J, Turecki G, Giros B*, Tzavara ET*. Antidepressive effects of targeting Elk-1 signal transduction. Nature Medicine, 2018, 24, 591-597. (*: corresponding authors).
- Guma E, Rocchetti J, Devenyi GA, Tanti A, Mathieu A, Lerch J, Elgbeili G, Courcot B, Mechawar N, Chakravarty MM & Giros B. Regional brain volume changes following chronic antipsychotic administration are mediated by the dopamine D2 receptor. Neuroimage, 2018, 176, 226-238.
|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
The high efficacy of muscarinic M4 receptor in D1 medium spiny neurons reverses striatal hyperdopaminergia. Neuropharmacology. 2019;146:74-83.
[Biological psychiatry v3.0]. Med Sci (Paris). 2018;34(11):899-900.
Antidepressive effects of targeting ELK-1 signal transduction. Nat Med. 2018;24(5):591-597.
Regional brain volume changes following chronic antipsychotic administration are mediated by the dopamine D2 receptor. Neuroimage. 2018;176:226-238.
Cocaine increases dopaminergic connectivity in the nucleus accumbens. Brain Struct Funct. 2017.
Regulation of the Hippocampal Network by VGLUT3-Positive CCK- GABAergic Basket Cells. Front Cell Neurosci. 2017;11:140.
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.