EPFL Brain Mind Institute (BMI), School of Life Sciences

Pierre Magistretti reviews tight metabolic coupling between astrocytes and neurons as a central feature of brain energy metabolism. His laboratory characterised two mechanisms: neuromodulator-induced glycogenolysis in astrocytes and glutamate-stimulated aerobic glycolysis, both releasing lactate that fuels neurons under the astrocyte-neuron lactate shuttle model. Lactate also acts as a signalling molecule that enhances NMDA receptor activity, promotes long-term memory and activates plasticity-related gene expression, and its astrocytic supply scales with activity and computational demand. Recent work shows lactate potentiates NMDA receptor currents through MCT-dependent neuronal uptake, conversion to pyruvate, increased NADH and redox-sensitive modulation of GluN2B subunits involving CaMKII. Preclinical studies in Glut1 deficiency syndrome, Alzheimer's disease and depression models suggest targeting astrocytes to overcome brain hypometabolism, opening therapeutic perspectives for neurodegenerative, mood and metabolic brain disorders.