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Véronique CHOUVET
Artist’s Rendering of an Astrocyte and Hydrogen Peroxide (H₂O₂) (Represented by White Particles)
At ESPCI Paris – PSL, a team of researchers led by Thomas Preat has discovered a crucial process linking neurons and a type of glial cell, astrocytes, in the formation of long-term memory. Published in Nature Metabolism, this study reveals a chemical cascade involving hydrogen peroxide (H₂O₂) synthesized by astrocytes—an unexpected key player. The discovery of this process—altered in a Drosophila model of Alzheimer’s disease that accumulates amyloid-β peptide—opens up highly promising new perspectives for deepening our understanding of this neurodegenerative disorder and considering the development of future treatments.
The study shows that long-term memory formation relies on a cascade of molecular interactions between astrocytes and neurons. During learning, acetylcholine, a neurotransmitter released by neurons, activates nearby astrocytes, leading to the enzymatic synthesis of hydrogen peroxide (H₂O₂). H₂O₂ is then imported into neurons in the mushroom body, the Drosophila olfactory memory center, where it triggers biochemical modifications essential for memory consolidation. In a Drosophila model of Alzheimer’s disease, the accumulation of human amyloid-β peptide blocks the synthesis of H₂O₂ by astrocytes, leading to cognitive decline.
At high concentrations, H₂O₂ is toxic to neurons due to its oxidative properties, and its levels are elevated in the brains of individuals with Alzheimer’s disease, a phenomenon known as oxidative stress. However, this research reveals that in small doses, H₂O₂ is essential for the formation of lasting memories.
This discovery enhances our understanding of astrocyte-neuron interactions, shedding light on the mechanisms involved in Alzheimer’s disease. By identifying a key process altered by the pathology, this research paves the way for new therapeutic strategies to combat cognitive decline.
Conducted at the Brain Plasticity Laboratory of ESPCI Paris – PSL and CNRS, this study is part of a broader research program exploring the links between energy metabolism and memory, funded by an ERC grant led by Thomas Preat. Its success is based on the use of Drosophila, a powerful biological model that provides an ideal research framework, offering faster and more flexible experimentation than rodent models.
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Reference :
Rabah, Y., Berwick, JP., Sagar, N. et al. Astrocyte-to-neuron H2O2 signalling supports long-term memory formation in Drosophila and is impaired in an Alzheimer’s disease model. Nat Metab (2025).
https://doi.org/10.1038/s42255-024-01189-3
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