"Neuron-glia metabolic coupling: relevance for neuronal plasticity and functional brain imaging"

Datum

18.09.2015

Zeit

11:00 - 12:00

Sprecher

Prof. Pierre Magistretti, Division of Biological and Environmental Sciences and Engineering, KAUST, Thuwal, KSA and Brain Mind Institute, EPFL, Lausanne, Switzerland

Sprache

en

Hauptthema

Biologie

Andere Themen

Biologie, Medizin

Host

Carlo V. Cannistraci

Beschreibung

A tight metabolic coupling between astrocytes and neurons is emerging as a key feature of brain energy metabolism (Bélanger et al 2011). 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 (Magistretti and Allaman, 2015). Second, the glutamate-stimulated aerobic glycolysis in astrocytes, mediated by the sodium-coupled reuptake of glutamate by astrocytes and the ensuing activation of the Na-K-ATPase, resulting in the release of lactate from astrocytes, which can then fuel the neuronal energy demands a mechanisms known as the Astrocyte Neuron Lactate Shuttle (ANLS).We have also recently shown that lactate derived from astrocytic glycogen is necessary for long-term memory consolidation and for maintenance of LTP (Suzuki et al, 2011). At the molecular level, 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 signalling cascade Erk1/2 (Yang et al, 2014). 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 signalling molecule for neuronal plasticity in addition to being an energy substrate.Publications: Magistretti PJ, Pellerin L, Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. Philos Trans R Soc Lond B Biol Sci. (1999) 354(1387):1155-63Suzuki A, Stern S.A, Bozdagi O, Huntley G.W, Walker R.H, Magistretti P.J*, Alberini C.M* (2011) Astrocyte-neuron lactate transport is required for long-term memory formation, Cell, 44(5):810-23 (*corresponding authors)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 (2014) Proc. Natl. Acad. Sci. U S A. 111(33):12228-1223 Lee Y, Morrison BM, Li Y, Lengacher S, Farah MH, Hoffman PN, Liu Y, Tsingalia A, Jin L, Zhang PW, Pellerin L, Magistretti PJ, Rothstein JD (2012) Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature, 487(7408):443-8. Magistretti PJ and Allaman I (2015) A cellular perspective on brain energy metabolism and imaging. Neuron, 86: 883 - 901

Links

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Letztmalig verändert: 18.09.2015, 09:44:49