Activity-dependent regulation of energy metabolism by astrocytes: an update.
Astrocytes play a critical role in the regulation of brain metabolic responses to activity. One detailed mechanism proposed to describe the role of astrocytes in some of these responses has come to be known as the astrocyte-neuron lactate shuttle hypothesis (ANLSH). Although controversial, the original concept of a coupling mechanism between neuronal activity and glucose utilization that involves an activation of aerobic glycolysis in astrocytes and lactate consumption by neurons provides a heuristically valid framework for experimental studies. In this context, it is necessary to provide a survey of recent developments and data pertaining to this model. Thus, here, we review very recent experimental evidence as well as theoretical arguments strongly supporting the original model and in some cases extending it. Aspects revisited include the existence of glutamate-induced glycolysis in astrocytes in vitro, ex vivo, and in vivo, lactate as a preferential oxidative substrate for neurons, and the notion of net lactate transfer between astrocytes and neurons in vivo. Inclusion of a role for glycogen in the ANLSH is discussed in the light of a possible extension of the astrocyte-neuron lactate shuttle (ANLS) concept rather than as a competing hypothesis. New perspectives offered by the application of this concept include a better understanding of the basis of signals used in functional brain imaging, a role for neuron-glia metabolic interactions in glucose sensing and diabetes, as well as novel strategies to develop therapies against neurodegenerative diseases based upon improving astrocyte-neuron coupled energetics.
Département de Physiologie, Université de Lausanne, Switzerland.
Luc
L
Pellerin
Unité de Résonance Magnétique des Systèmes Biologiques, UMR5536 CNRS-Université Victor Segalen, Bordeaux, France.
Anne-Karine
AK
Bouzier-Sore
Département de Physiologie, Université de Lausanne, Switzerland.
Agnès
A
Aubert
Unité de Résonance Magnétique des Systèmes Biologiques, UMR5536 CNRS-Université Victor Segalen, Bordeaux, France.
Sébastien
S
Serres
Unité de Résonance Magnétique des Systèmes Biologiques, UMR5536 CNRS-Université Victor Segalen, Bordeaux, France.
Michel
M
Merle
INSERM U678, Université Pierre et Marie Curie-Paris 6, Paris, France.
Robert
R
Costalat
Brain and Mind Institute, Ecole Polytechnique Fédérale de Lausanne and Centre de Neurosciences Psychiatriques, Hôpital de Cery, Prilly, Switzerland.
Pierre J
PJ
Magistretti
D000332:Aerobiosis; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000502:physiology*; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology; D006019:Glycolysis / Q000502:physiology; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D015233:Models, Statistical; D009474:Neurons / Q000378:metabolism
D019344:Lactic Acid; D018698:Glutamic Acid