Laboratory of Neuroenergetics and Psychiatric Diseases

The research unit of Prof. Pierre Magistretti is dedicated to studying the role of astrocytes, neuroenergetics and neurometabolic coupling in psychiatric diseases and addiction.

Previous work from Magistretti’s laboratory have shown that under metabolic demand, neurons signal to astrocytes to undergo two different mechanisms to provide a source of energy, 1- increased glycogenolysis (energy reserve found solely in astrocytes) or 2-increased aerobic glycolysis. Activation of these pathways produce lactate which can be used as a source of energy for neurons. This mechanism, referred as Astrocyte Neuron Lactate Shuttle (ANLS), is shown to be involved in basic neuro-physiological functions such as learning and memory and across sleep-wake cycle.

Given that patients with psychiatric diseases show losses in astrocyte numbers and have impairments in glucose utilizations, we hypothesize that a dysfunction of this brain energy metabolic coupling could play a role in the etiology of the illnesses.

• Impact of various antidepressants drug on brain energy metabolism in vitro.
• Involvement of brain energy metabolism in antidepressant effects of pharmacological or environmental manipulations (sleep deprivation, stress) in vivo.
• Role of brain energy metabolism in animal models of addiction (rodents).

These projects are carried out in collaboration with Drs Benjamin Boutrel, Jean-Luc Martin, Jean-René Cardinaux and Jean-Marie Petit at the CNP. Axis 1 and 2 are performed in the framework of the « Pôle de Recherche National (PRN) Synapsy, (NCCR “The synaptic bases of the mental diseases”) funded by the “Fonds National Suisse de la Recherche Scientifique” and supported by the "Fondation Préfargier".

• Examining the impact of various antidepressants drugs on brain energy metabolism in vitro.
  Cell cultures of astrocytes and neurons represent a good strategy to study the impact of antidepressants on brain energy metabolism and to dissect out the mechanism of action in different cell types. Towards the end of the experiment, cells and their media are harvested and evaluated for their metabolic, kinetic and molecular profiles using specific assays designed towards each end.

• Determining the involvement of brain energy metabolism in antidepressant effects of pharmacological or environmental manipulations in vivo.
  Biosensor is a highly sensitive technique with a great time resolution and is used to detect brain metabolic products in freely moving animals.

Original articles

• Peripheral administration of lactate produces antidepressant-like effects.
  Carrard A, Elsayed M, Margineanu M, Boury-Jamot B, Fragnière L, Meylan EM, Petit JM, Fiumelli H, Magistretti PJ*, Martin JL*.
  Mol Psychiatry. 2016 Dec 6. doi: 10.1038/mp.2016.237.

• Astrocyte β2-adrenergic receptors mediate hippocampal long-term memory consolidation.
  Gao V, Suzuki A, Magistretti PJ, Lengacher S, Pollonini G, Steinman MQ, Alberini CM.
  Proc Natl Acad Sci U S A. 2016 Jul 26;113(30):8526-31. doi: 10.1073/pnas.1605063113

• Disrupting astrocyte-neuron lactate transfer persistently reduces conditioned responses to cocaine.
  Boury-Jamot B, Carrard A, Martin JL, Halfon O, Magistretti PJ*, Boutrel B.*
  Mol Psychiatry. 2015 Oct 27. doi: 10.1038/mp.2015.157. [Epub ahead of print]

• Glutamate Cysteine Ligase-Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage.
  Lavoie S, Steullet P, Kulak A, Preitner F, Do KQ, Magistretti PJ.
  Front Physiol. 2016 Apr 21;7:142. doi: 10.3389/fphys.2016.00142. eCollection 2016.

• A Role for Lactate in the Consolidation of Drug-Related Associative Memories.
  Boutrel B, Magistretti PJ.
  Biol Psychiatry. 2016 Jun 1;79(11):875-7. doi: 10.1016/j.biopsych.2016.04.010.

• The HDAC inhibitor SAHA improves depressive-like behavior of CRTC1-deficient mice: Possible relevance for treatment-resistant depression.
  Meylan EM, Halfon O, Magistretti PJ, Cardinaux JR.
  Neuropharmacology. 2016 Mar 9;107:111-121. doi: 10.1016/j.neuropharm.2016.03.012.

• L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade.
  Jourdain P, Allaman I, Rothenfusser K, Fiumelli H, Marquet P, Magistretti PJ.
  Sci Rep. 2016 Feb 19;6:21250. doi: 10.1038/srep21250.

• The Subjective Sensation of Synchrony: An Experimental Study.
  Llobera J, Charbonnier C, Chagué S, Preissmann D, Antonietti JP, Ansermet F, Magistretti PJ.
  PLoS One. 2016 Feb 12;11(2):e0147008. doi: 10.1371/journal.pone.0147008. eCollection 2016.

• In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons.
  Mächler P, Wyss MT, Elsayed M, Stobart J, Gutierrez R, von Faber-Castell A, Kaelin V, Zuend M, San Martín A, Romero-Gómez I, Baeza-Lehnert F, Lengacher S, Schneider BL, Aebischer P, Magistretti PJ, Barros LF, Weber B.
  Cell Metab. 2016 Jan 12;23(1):94-102. doi: 10.1016/j.cmet.2015.10.010.

• Learning-Induced Gene Expression in the Hippocampus Reveals a Role of Neuron -Astrocyte Metabolic Coupling in Long Term Memory.
  Tadi M, Allaman I, Lengacher S, Grenningloh G, Magistretti PJ.
  PLoS One. 2015 Oct 29;10(10):e0141568. doi: 10.1371/journal.pone.0141568. eCollection 2015.

• Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2.
  Kovács KA, Steinmann M, Halfon O, Magistretti PJ, Cardinaux JR.
  Cell Signal. 2015 Nov;27(11):2252-60. doi: 10.1016/j.cellsig.2015.08.001.

• Three-dimensional immersive virtual reality for studying cellular compartments in 3D models from EM preparations of neural tissues.
  Calì C, Baghabra J, Boges DJ, Holst GR, Kreshuk A, Hamprecht FA, Srinivasan M, Lehväslaiho H, Magistretti PJ.
  J Comp Neurol. 2016 Jan 1;524(1):23-38. doi: 10.1002/cne.23852.

• Embodied memory: unconscious smiling modulates emotional evaluation of episodic memories.
  Arminjon M, Preissmann D, Chmetz F, Duraku A, Ansermet F, Magistretti PJ.
  Front Psychol. 2015. 6:650. doi: 10.3389/fpsyg.2015.00650.

• Metabolic gene expression changes in astrocytes in Multiple Sclerosis cerebral cortex are indicative of immune-mediated signaling.
  Zeis T, Allaman I, Gentner M, Schroder K, Tschopp J, Magistretti PJ, Schaeren-Wiemers N.
  Brain Behav Immun. 2015. 48:313-25. doi: 10.1016/j.bbi.2015.04.013.

• Channel-mediated lactate release by K⁺-stimulated astrocytes.
  Sotelo-Hitschfeld T, Niemeyer MI, Mächler P, Ruminot I, Lerchundi R, Wyss MT, Stobart J, Fernández-Moncada I, Valdebenito R, Garrido-Gerter P, Contreras-Baeza Y, Schneider BL, Aebischer P, Lengacher S, San Martín A, Le Douce J, Bonvento G, Magistretti PJ, Sepúlveda FV, Weber B, Barros LF.
  J Neurosci. 2015. 35(10):4168-78. doi: 10.1523/JNEUROSCI.5036-14.2015.

• Multi-timescale modeling of activity-dependent metabolic coupling in the neuron-glia-vasculature ensemble.
  Jolivet R, Coggan JS, Allaman I, Magistretti PJ.
  PLoS Comput Biol. 2015. 11(2):e1004036. doi: 10.1371/journal.pcbi.1004036.

• Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush.
  Morrison BM, Tsingalia A, Vidensky S, Lee Y, Jin L, Farah MH, Lengacher S, Magistretti PJ, Pellerin L, Rothstein JD.
  Exp Neurol. 2015. 263:325-38. doi: 10.1016/j.expneurol.2014.10.018.

• Sustained sleep fragmentation induces sleep homeostasis in mice.
  Baud MO, Magistretti PJ, Petit JM.
  Sleep. 2015. 38(4):567-79. doi: 10.5665/sleep.4572.

• Control of mitochondrial pH by uncoupling protein 4 in astrocytes promotes neuronal survival.
  Perreten Lambert H, Zenger M, Azarias G, Chatton JY, Magistretti PJ, Lengacher S.
  J Biol Chem. 2014 Nov 7;289(45):31014-28. doi: 10.1074/jbc.M114.570879

• Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons.
  Yang J, Ruchti E, Petit JM, Jourdain P, Grenningloh G, Allaman I, Magistretti PJ.
  Proc Natl Acad Sci U S A. 2014. 111(33):12228-33. doi: 10.1073/pnas.1322912111

• Hypertonic lactate and the injured brain: facts and the potential for positive clinical implications.
  Bouzat P, Magistretti PJ, Oddo M.
  Intensive Care Med. 2014. 40(6):920-1. doi: 10.1007/s00134-014-3312-x

• Increased activation in Broca's area after cognitive remediation in schizophrenia.
  Vianin P, Urben S, Magistretti P, Marquet P, Fornari E, Jaugey L.
  Psychiatry Res. 2014. 221(3):204-9. doi: 10.1016/j.pscychresns.2014.01.004.

• Cerebral metabolic effects of exogenous lactate supplementation on the injured human brain.
  Bouzat P, Sala N, Suys T, Zerlauth JB, Marques-Vidal P, Feihl F, Bloch J, Messerer M, Levivier M, Meuli R, Magistretti PJ, Oddo M.
  Intensive Care Med. 2014. 40(3):412-21. doi: 10.1007/s00134-013-3203-6.

• The human CFTR protein expressed in CHO cells activates aquaporin-3 in a cAMP-dependent pathway: study by digital holographic microscopy.
  Jourdain P, Becq F, Lengacher S, Boinot C, Magistretti PJ, Marquet P.
  J Cell Sci. 2014. 127(Pt 3):546-56. doi: 10.1242/jcs.133629

Reviews

• Sodium signaling and astrocyte energy metabolism.
  Chatton JY, Magistretti PJ, Barros LF.
  Glia. 2016 Oct;64(10):1667-76. doi: 10.1002/glia.22971.

• A New Outlook on Mental Illnesses: Glial Involvement Beyond the Glue.
  Elsayed M, Magistretti PJ.
  Front Cell Neurosci. 2015 Dec 16;9:468. doi: 10.3389/fncel.2015.00468. eCollection 2015. Review.

• Regulation of neuron-astrocyte metabolic coupling across the sleep-wake cycle.
  Petit JM, Magistretti PJ.
  Neuroscience. 2016 May 26;323:135-56. doi: 10.1016/j.neuroscience.2015.12.007. Epub 2015 Dec 17. Review.

• Astrocytes: New Targets for the Treatment of Neurodegenerative Diseases.
  Finsterwald C, Magistretti PJ, Lengacher S.
  Curr Pharm Des. 2015;21(25):3570-81.

• A cellular perspective on brain energy metabolism and functional imaging.
  Magistretti PJ, Allaman I.
  Neuron. 2015. 86(4):883-901. doi: 10.1016/j.neuron.2015.03.035. Review.

• Methylglyoxal, the dark side of glycolysis.
  Allaman I, Bélanger M, Magistretti PJ.
  Front Neurosci. 2015. 9:23. doi: 10.3389/fnins.2015.00023.

• Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect.
  Demetrius LA, Magistretti PJ, Pellerin L.
  Front Physiol. 2015. 5:522. doi: 10.3389/fphys.2014.00522.

• Review of quantitative phase-digital holographic microscopy: promising novel imaging technique to resolve neuronal network activity and identify cellular biomarkers of psychiatric disorders.
  Marquet P, Depeursinge C, Magistretti PJ.
  Neurophotonics. 2014. 1(2):020901. doi: 10.1117/1.NPh.1.2.020901

• Glycogen metabolism and the homeostatic regulation of sleep.
  Petit JM, Burlet-Godinot S, Magistretti PJ, Allaman I.
  Metab Brain Dis. 2015. 30(1):263-79. doi: 10.1007/s11011-014-9629-x.