Astrocytic mitochondrial ROS modulate brain metabolism and mouse behaviour

Nature Metabolism
Carlos Vicente-GutierrezJuan P Bolaños

Abstract

To satisfy its high energetic demand1, the brain depends on the metabolic cooperation of various cell types2-4. For example, astrocytic-derived lactate sustains memory consolidation5 by serving both as an oxidizable energetic substrate for neurons6 and as a signalling molecule7,8. Astrocytes and neurons also differ in the regulation of glycolytic enzymes9 and in the organization of their mitochondrial respiratory chain10. Unlike neurons, astrocytes rely on glycolysis for energy generation9 and, as a consequence, have a loosely assembled mitochondrial respiratory chain that is associated with a higher generation of mitochondrial reactive oxygen species (ROS)10. However, whether this abundant natural source of mitochondrial ROS in astrocytes fulfils a specific physiological role is unknown. Here we show that astrocytic mitochondrial ROS are physiological regulators of brain metabolism and neuronal function. We generated mice that inducibly overexpress mitochondrial-tagged catalase in astrocytes and show that this overexpression decreases mitochondrial ROS production in these cells during adulthood. Transcriptomic, metabolomic, biochemical, immunohistochemical and behavioural analysis of these mice revealed alterations in brain re...Continue Reading

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Citations

Jan 29, 2020·Neurochemical Research·Carlos Vicente-GutiérrezRubén Quintana-Cabrera
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Methods Mentioned

BETA
transgenic
flow cytometry
PCR
nuclear translocation
genotyping
transfection
Assay
electrophoresis
X-Ray
confocal microscopy

Software Mentioned

Affymetrix Transcriptome Analysis Console ( TAC )
Limma
MetaboAnalyst
Database for Annotation , Visualization and Integrated Discove...
maze
Adobe Photoshop
Excel
AMi
Integrated Molecular Pathway Level Analysis ( IMPaLA
ImageJ

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