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Luc PellerinSynaptic plasticity = Metabolic plasticity ? Regulation of monocarboxylate transporter expression by signals linked to neuronal activity

Abstract :


Molecular mechanisms of synaptic plasticity have been the subject of intense investigations over the last two decades.
A quite complex description of the different proteins involved, their interactions as well as the regulation of their expression and localization has been provided for different processes contributing to synaptic plasticity in different structures of the central nervous system.

However, one domain that has not received much attention concerns the energetic aspects pertaining to the modifications of synaptic strength. A few years ago, a new model of brain energetics has emerged which involves lactate transfer between astrocytes and neurons. In this context, the role of monocarboxylate transporters in regulating lactate supply to neurons as an alternative energy substrate appears critical. Data will be presented showing that the neurotrophin BDNF has a dual effect on MCT2, the main monocarboxylate transporters expressed by neurons.

First, it causes the translocation of MCT2 to the plasma membrane of cultured neurons, a phenomenon that is analogous to the translocation of the AMPA receptor subunits GluR1 and GluR2. Moreover, BDNF was found to enhance MCT2 expression, both in vitro and in vivo, by a mechanism involving a translational regulation.

In parallel, we have observed that NO induces the expression of MCT4 in cultured astrocytes by a translational mechanism, an effect that facilitates lactate release. These observations suggest that coordinate mechanisms are initiated by neuronal signals produced usually in the context of synaptic plasticity that concur to promote energy supply.

Selected publications

Comment on recent modeling studies of astrocyte-neuron metabolic interactions. Jolivet R, Allaman I, Pellerin L, Magistretti PJ, Weber B. Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland. J Cereb Blood Flow Metab. 2010 Aug 11. [Epub ahead of print]

The anorexigenic effects of metformin involve increases in hypothalamic leptin receptor expression. Aubert G, Mansuy V, Voirol MJ, Pellerin L, Pralong FP.Metabolism. 2010 Mar 17. 

Scientific focus :

Luc Pellerin dirige un groupe dont la thématique porte sur les transporteurs aux monocarboxylates et leur rôle dans le maintien de l'homéostasie énergétique, principalement au niveau cérébral.

Sophie Layé