Pierre J. Magistretti, received his MD in 1979 from the University of Geneva and his PhD in Biology in 1982 from UCSD. He is Distinguished Professor and Dean at the Division at Biological and Environmental Sciences and Engineering at KAUST; he also has an affiliation at the Brain Mind Institute at EPFL. Pierre Magistretti's laboratory has discovered some of the cellular and molecular mechanisms that underlie the coupling between neuronal activity and energy consumption by revealing the key role that glial cells, in particular astrocytes, play in this physiological process. These findings are particularly relevant for understanding the origin of the signals detected by functional brain imaging, and are revealing a role of astrocytes in neuronal plasticity and neuroprotection.
He is the author of over 240 publications in international peer-reviewed journals and has given over 60 invited lectures during the past five years.
He has been elected at the International Chair 2007-2008 of the Collège de France, Paris. He is member of Academia Europae and of the Swiss Academy of Medical Sciences. Among other recognitions, Pierre Magistretti has been awarded the Camillo Golgi Medal Award, the Emil Kraepelin Professorship, the Goethe Award of the Canadian Psychological Association and the Ott Prize of the Swiss Academy of Medical Sciences. Recently, he shared with David Attwell and Marcus Raichle the 2016 IPSEN Foundation Prize. Pierre Magistretti is a honorary member of the Chinese Association of Physiological Sciences.
He is the Past-President of the Federation of European Neuroscience Societies (FENS) and Past‐Secretary General of the International Brain Research Organization (IBRO) of which he is now President since 2014. He is on the Board of Trustees of HFSPO and a Fellow of the American College of Psychopharmacology. He is and has been member of several academic scientific advisory boards including the Research Council of the Swiss National Science Foundation. He is member of the Dana Alliance for Brain Initiatives (DABI) and in this capacity he is strongly engaged in the public understanding of neuroscience.
metabolic coupling : role in neuronal plasticity, memory and neuroprotection
A tight metabolic coupling between astrocytes and neurons is a key feature of brain energy metabolism (Bélanger et al Cell Metab 2011; Magistretti and Allaman, Neuron 2015). Over the years we have described two basic mechanisms of neurometabolic coupling. First the glycogenolytic effect of VIP - restricted to cortical columns - and of noradrenaline - spanning across functionally distinct cortical areas - indicating a regulation of brain homeostasis by neurotransmitters acting on astrocytes, as glycogen is exclusively localized in these cells. Second, the glutamate-stimulated aerobic glycolysis in astrocytes. This metabolic response is mediated by the sodium-coupled reuptake of glutamate by astrocytes and the ensuing activation of the Na-K-ATPase. This results in the release of lactate from astrocytes, which can then fuel the neuronal energy demands a mechanisms known as the ANLS (for review see Pellerin and Magistretti JCBFM 2011). The ANLS model provides a direct mechanism to couple synaptic activity with glucose use and is consistent with the notion that the signals detected during physiological activation with 18F-deoxyglucose (DG)-PET may reflect predominantly uptake of the tracer into astrocytes. This conclusion does not question the validity of the 2-DG-based techniques, rather it provides a cellular and molecular basis for these functional brain imaging techniques.
We have recently revealed a second function of lactate, as a signaling molecule for plasticity. Indeed we have shown that lactate derived from astrocytic glycogen is necessary for long-term memory consolidation and for induction in neurons of plasticity genes such as Arc and for maintenance of LTP (Suzuki et al, Cell 2011). We therefore set out to investigate the molecular mechanisms at the basis of the function of L-lactate on neuronal plasticity. We have found that L-lactate stimulates the expression of synaptic plasticity-related genes such as Arc, Zif268 and BDNF through a mechanism involving NMDA receptor activity and its downstream signaling cascade Erk1/2 (Yang et al, PNAS 2014). L-lactate potentiates NMDA receptor-mediated currents and the ensuing increases in intracellular calcium. In parallel to this, L-lactate increases intracellular levels of NADH hence modulating the redox state of neurons. NADH mimicks all the effects of L-lactate on NMDA signaling, pointing to NADH increase as a primary mediator of L-lactate effects. Effects on plasticity gene expression are observed both in primary neurons in culture and in vivo in the sensory-motor cortex. These results provide novel insights for the understanding of the molecular mechanisms underlying the critical role of astrocyte-derived L-lactate in long term memory and reveal a novel action of L-lactate as a signaling molecule for neuronal plasticity.
Using a fully immersive virtual reality (VR) environment (CAVE, cave automatic virtual environment) in which 3D electron microscopy stacks were reconstructed and segmented for the different cellular and subcellular elements in the rat hippocamous, we observed a nonrandom distribution of glycogen granules, with a high enrichment around synaptic boutons (Cali et al J. Comp. Neurol. 2016).