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Sv - BMI
INSTITUTE Aebischer, Patrick
Blanke, Olaf
Hirling, Harald
Fraering, Patrick
Gerstner, Wulfram
Hadjikhani, Nouchine
Herzog, Michael
Lüthi-Carter, Ruth
Lashuel, Hilal
Magistretti, Pierre
Markram, Henry
Moore, Darren
Petersen, Carl
Sandi, Carmen
Schneggenburger, Ralf
PUBLICATIONS LIST
P. Magistretti
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Laboratory of Neuroenergetics and Cellular Dynamics
Pierre Magistretti, MD., Ph.D.
Professor
BMI Director
Research Interests
Research in the Laboratory of Neuroenergetics and Cellular Dynamics is centered around the understanding of the cellular and molecular mechanisms of brain energy metabolism. The key question addressed is how the energetic demands related to neuronal function are met in register with synaptic activity. We have identified a set of mechanisms centered around the role of astrocytes in coupling synaptic signals mediated by glutamate to the entry of glucose into the brain parenchyma and the provision of energy substrates to restore the energy budget of neurons. We have also characterized another aspect of neurotransmitter-regulated energy metabolism, namely that related to glycogen mobilization in register to neuronal activity. These results have a particular relevance to functional brain imaging as they have provided the cellular and molecular bases for the understanding of the signals detected by these imaging techniques during activation of specific neuronal pathways. Another temporal dimension of neuronal activity is one related to the mechanisms of synaptic plasticity which are expressed over prolonged time-scales up to hours or days and which are though to underlie the processes of learning and memory. Accordingly, we are now addressing the issue of "metabolic plasticity". Indeed, it is very likely that metabolic adaptations do occur in register with the functional and structural changes that occur during synaptic plasticity. We are currently studying transcriptionally-regulated adaptations in the level of expression of certain genes of brain energy metabolism in relation to synaptic plasticity as observed during learning, the sleep-wake cycle and addiction.
We are also interested in on-line imaging microscopic techniques that allow the visualization of dynamic cellular processes, including those involved in plasticity. We collaborate with LNC and with the Advanced Photonics Laboratory at the STI Faculty, in the application of digital holographic microscopy combined with atomic force microscopy, fluorescence microscopy and other coherent imaging approaches.
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Key Publications
Wyss MT, Weber B, Treyer V, Heer S, Pellerin L, Magistretti PJ, Buck A. "Stimulation-induced increases of astrocytic oxidative metabolism in rats and humans investigated with 1-11 C-acetate." J Cereb Blood Flow Metab. 2009 Jan;29(1): 44-56.Epub 2008 Aug 20.
B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, "Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer," Cytometry Part A 73A, 895-903 (2008).
Rappaz B, Barbul A, Emery Y, Korenstein R, Depeursinge C, Magistretti PJ, Marquet P. Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer. Cytometry A. 2008 Jul 9. [Epub ahead of print]
Chiry O, Fishbein WN, Merezhinskaya N, Clarke S, Galuske R, Magistretti PJ, Pellerin L. Distribution of the monocarboxylate transporter MCT2 in human cerebral cortex: An immunohistochemical study. Brain Res. 2008 Jun 18
Badaut J, Brunet JF, Petit JM, Guérin CF, Magistretti PJ, Regli L.Induction of brain aquaporin 9 (AQP9) in catecholaminergic neurons in diabetic rats. Brain Res. 2008 Jan 10; 1188:17-24. Epub 2007 Nov 7
Rappaz B, Charrière F, Depeursinge C, Magistretti PJ, Marquet P. Simultaneous cell morphometry and refractive index measurement with dual-wavelength digital holographic microscopy and dye-enhanced dispersion of perfusion medium. Opt Lett. 2008 Apr 1; 33(7):744-6.
Gavillet M, Allaman I, Magistretti PJ. Modulation of astrocytic metabolic phenotype by proinflammatory cytokines. Glia. 2008 Mar 27; [Epub ahead of print]
Ros J, Pellerin L, Magara F, Daughet J, Schenk F, Magistretti P.J.(2006) Metabolic activation pattern of distinct hippocampal subregions during spatial learning and memory retrival. J. Cereb. Blood Flow Metab. 2006 Apr; 26(4):468-77
Marquet, P., Rappaz, B., Magistretti, P.J., Cuche, E., Emery, Y., Colomb, T., Depeursinge, C. (2005) Digital holographic microscopy : a noninvasive contrast imaging technique allowing quantitative visualization of living cells with subwavelength axial accuracy. Optics Letters 30 : 468-470.
Ros J, Pellerin L, Magara F, Dauguet J, Schenk F, Magistretti PJ. Metabolic activation pattern of distinct hippocampal subregions during spatial learning and memory retrieval. J Cereb Blood Flow Metab. (Advance online publication, 31 August 2005)
Bliss, T.M., Ip, M., Cheng, E., Minami, M., Pellerin, L., Magistretti, P.J., Sapolsky, R.M. (2004) Dual-gene, dual-cell type therapy against an excitotoxic insult by bolstering neuroenergetics. J. Neurosci. 24, 6202-6208. Bernardinelli, Y., Magistretti, P.J., Chatton, J.-Y. Astrocytes generate Na+-mediated metabolic waves (2004) Proc. Natl. Acad. Sci. USA 101 : 14937-42.
Pellerin, L. and Magistretti, P.J. (2004) Let there be (NADH) light. Science 305, 50-52.
Voutsinos-Porche, B., Bonvento, G., Tanaka, K., Steiner, P., Welker, E., Chatton, J.-A., Magistretti, P.J. and Pellerin, L. (2003) Glial glutamate transporters mediate a functional metabolic crosstalk between neurons and astrocytes in the mouse developing cortex. Neuron, 37, 1-20.
Petit, J.M., Tobler, I., Allaman, I., Borbély, A.A. and Magistretti, P.J. (2002) Sleep deprivation modulates brain mRNAs encoding genes of glycogen metabolism. Eur. J. Neurosci. 16, 1163-1167.
Magistretti, P.J. and Pellerin, L. (1999) Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. Phil. Trans. R. Soc. London. B, 354 : 1155-1163
Pellerin, L. and Magistretti, P.J. (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis : A mechanism coupling neuronal activity to glucose utilization Proc. Natl. Acad. Sci. (USA) , 91 : 10625 - 10629
Magistretti P.J. and Schorderet, M. (1984) VIP and noradrenaline act synergistically to increase cyclic AMP in cerebral cortex Nature 308, 280-282
Magistretti P.J., Morrison, J.H., Shoemaker, W.J., Sapin, V. and Bloom, F.E. (1981) Vasoactive intestinal polypeptide induced glycogenolysis in mouse cortical slices : a possible regulatory mechanism for the local control of energy metabolism. Proc. Natl. Acad. Sci. USA 78, 6535-6539
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