Astrocyte-Neuron Lactate Shuttle: from proof-of-concept to a major paradigm shift in neuroenergetics
Department of Physiology, University of Lausanne, Bordeaux, France
Glucose is considered the main if not exclusive energy source for the adult brain. Moreover, neurons are the major energy consumers in the brain and it was assumed that they are fueled essentially by the complete oxidation of glucose. Twenty-five years ago, the Astrocyte-Neuron Lactate Shuttle hypothesis challenged this view. Based initially on in vitro experiments, it proposed that astrocytes would respond to neuronal activity by enhancing their uptake of glucose and release of lactate. In parallel, neurons would take advantage of lactate availability and use it as an additional energy substrate, especially during periods of activity. A direct implication of this concept is the fact that the origin of brain imaging signals based on the use of the glucose analog deoxyglucose is the astrocyte (not neurons) although it reflects neuronal activity. The demonstration of the validity of this model, particularly in vivo, proved to be arduous and gave rise to strong controversy in the field. Nevertheless, key evidence were obtained with different approaches. From the use of transgenic animals (e.g. glutamate and monocarboxylate transporter knockout or knockdown animals) and of different cutting edge techniques (e.g. Positron Emission Tomography, NMR or BOLD fMRI), it has become clear that the main tenets of the model hold true. Nowadays, the importance of this concept is tested in various physiological (e.g. learning and memory) and pathological (e.g. neurodegenerative diseases) contexts.
Host: Vanja Tepavcevic