Professor Pierre Magistretti
Photo Credit: Courtesy of Abdullah University of Science and Technology
Scientific Frontline: Extended "At a Glance" Summary: Astrocyte-Neuron Lactate Signaling
The Core Concept: Astrocytes, the star-shaped glial cells in the brain, actively shuttle lactate to neurons not only as an energy source but as a critical signaling molecule that modulates cellular chemistry and cements learning and memory.
Key Distinction/Mechanism: Deviating from the traditional view that lactate is merely a metabolic byproduct, this mechanism demonstrates that incoming lactate is converted into pyruvate within neurons, generating NADH. This shifts the cellular chemical balance to boost calcium signaling, tightening enzyme activity on NMDA receptors and driving lasting changes in synaptic connection strength.
Major Frameworks/Components:
- Astrocytes: Glial support cells that continuously produce and distribute lactate across neural networks.
- Lactate-to-Pyruvate Conversion: The intracellular metabolic reaction that produces NADH, altering the neuron's chemical equilibrium.
- Calcium Signaling Cascade: A cellular process amplified by the NADH shift, essential for intercellular communication.
- NMDA Receptors: Synaptic proteins governed by neurotransmitters and amplified by astrocyte-derived lactate, directly responsible for driving long-term synaptic plasticity.
Branch of Science: Neuroscience, Neurobiology, Neurochemistry, and Cellular Biology.
Future Application: Modulating astrocyte-specific metabolic pathways and NMDA receptor interactions offers potential therapeutic pathways for neurodegenerative and psychiatric conditions, including Alzheimer's disease, major depression, and schizophrenia.
Why It Matters: This discovery dismantles over a century of neuroscientific orthodoxy by elevating glial cells from structural "brain glue" to integral cognitive processing units, providing profound mechanistic insights into neural connectivity and memory formation.
Scientists at King Abdullah University of Science and Technology (KAUST) have uncovered the role that astrocytes, a type of non-neuronal cell called glia, play in communication between neurons and in processes linked to learning and memory.
While astrocytes have long been known to provide energy to neurons, whether they also shape signaling between neurons has remained unclear—until now.
Published in The Journal of Physiology, a new KAUST study shows that the same molecule involved in muscle metabolism, lactate, not only acts as a source of energy but also triggers a signaling pathway in neurons.
The findings challenge the traditional view of astrocytes as passive support cells by showing they play an active role in regulating communication between neurons. They provide new insight into the molecular mechanisms that support communication between brain cells and highlight the active role of astrocytes in shaping synaptic plasticity, said Professor Pierre Magistretti, principal investigator of the KAUST Laboratory of Cellular Imaging and Energetics.
“This observation represents a paradigm shift,” he said. “It shows that glial metabolism is an integral part of information processing by neurons, with implications for learning and memory.”
Magistretti, who is also the Ibn Sina Distinguished Professor of Bioscience and vice president for research at KAUST, added that his team demonstrates how the process works when lactate enters neurons and triggers a cascade of molecular events that enable key protein interactions at synapses—the sites where neurons connect and exchange information.
While neuroscientists already knew that lactate fueled neurons through a process described by Magistretti several years ago known as the astrocyte-neuron lactate shuttle, this study shows it also directly influences how neurons signal to one another at synapses. This matters because the disruption of synaptic communication is involved in conditions such as memory loss and several neurological disorders.
Conducted largely at KAUST, the study involved an international collaboration with the University of Milan in Italy and Lausanne University Hospital in Switzerland. This research brought together complementary expertise in cellular imaging, electrophysiology, molecular biology, and synaptic physiology.
The study has clear relevance for the neuroscience community in Saudi Arabia and globally, Magistretti noted. It addresses fundamental questions about how brain energy metabolism shapes neuronal communication and memory formation.
Given the role of synaptic communication in learning, memory, and several neurological and psychiatric disorders, these findings open new avenues for therapeutic strategies targeting these processes, he added. “The work highlights KAUST’s role in advancing research that connects fundamental brain science to real-world health challenges.”
Published in journal: The Journal of Physiology
Authors: Hubert Fiumelli, Gabriel Herrera-López, Fouad Lemtiri-Chlieh, Lorène Mottier, John Girgis, Carine Ben-Adiba, Pascal Jourdain, Nicolò Carrano, Hanan Mahmood, Amanda Ooi, Stefan T. Arold, Monica Di Luca, Fabrizio Gardoni, and Pierre J. Magistretti
Source/Credit: Abdullah University of Science and Technology
Edited by: Scientific Frontline
Reference Number: ns060426_02