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The metabolic cooperation of astrocytes and neurons fashions brain activity

In a review published in Cell Metabolism, Gilles Bonvento (LMN/MIRCen/CEA-Jacob) and Juan P. Bolaños (IBFG/University of Salamanca) present the latest findings on astrocyte-neuron metabolic cooperation and how it affects brain function.

Published on 3 August 2021

The human brain consumes about 20% of the body's nutrient and oxygen uptake continuously, as it has no energy reserve mechanism.

This energy-hungry organ is the control center of the human body and thus the mechanisms ensuring its metabolism must be strictly regulated.

Data published over the last several years show that astrocytes, a type of glial cell, play a fundamental role in this process by exchanging metabolites (small molecules) with neurons, ensuring an energy supply while also modulating inter-neuronal synaptic activity.

Astrocytes are thus essential partners for neurons, regulating not only their function but also their plasticity, which is essential for the cognitive activity of the human brain. It has been clearly shown that perturbations affecting this metabolic cooperation contribute to the initiation or progression of several neurological diseases, which, in turn, clearly illustrates the need for innovative therapies to ensure the supply of energy to the brain.

In a work published in Cell Metabolism, Gilles Bonvento (LMN/MIRCen/CEA/CNRS/Paris-Saclay University) and Juan P. Bolãnos (IBFG/University of Salamanca/CIBERFES) provide a review of the latest data on this subject.

In the brain, excitable cells that generate an action potential and activate synaptic connections preferentially use mitochondrial oxidative phosphorylationᵃ to cover their metabolic needs. That metabolic activity can fragilize neurons. However, research has shown that a cellular alliance comprising neurons and astrocytes is able to address that vulnerability. As part of this cellular cooperation, glycolytic enzymes are stimulated in the astrocytes, where the mitochondrial respiratory chain is, in terms of bioenergy, less well organized than it is in neurons.

These two cell types are metabolically paired to ensure neurotransmission energy needs, but that is not all. Astrocytes also convert glucose into numerous intermediaries, some of which may be transported inside the neurons and contribute directly to neurotransmission regulation. L-serin is an example of a metabolite produced only by the astrocytes, and studies¹ done by G. Bonvento's team have demonstrated the role of that amino acid in neuronal plasticity and an alteration of its astrocyte-to-neuron transfer in Alzheimer's disease.

The authors conclude their review by underlining the importance of more precisely characterizing the mechanisms that regulate this metabolic alliance in vivo. Such knowledge will enable the identification of still-undiscovered actors of cerebral energy balance and function, in both normal and pathological conditions, and the discovery of new therapeutic possibilities easily transferred to the patient's bedside.

a : Mitochondrial oxidative phosphorylation is the last phase of aerobic cellular respiration. It occurs on the inner mitochondrial membrane. Cellular respiration describes the entirety of metabolic processes needed to transform glucose into cellular energy in the form of ATP.

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