Whole-brain neuronal MCT2 lactate transporter expression links metabolism to human brain structure and function
Loading...
Date
2022
Journal Title
Journal ISSN
Volume Title
Publisher
National Academy of Sciences
PNAS
PNAS
Abstract
Brain activity is constrained by local availability of chemical energy, which is generatedthrough compartmentalized metabolic processes. By analyzing data of whole humanbrain gene expression, we characterize the spatial distribution of seven glucose andmonocarboxylate membrane transporters that mediate astrocyte–neuron lactate shuttletransfer of energy. We found that the gene coding for neuronal MCT2 is the onlygene enriched in cerebral cortex where its abundance is inversely correlated withcortical thickness. Coexpression network analysis revealed that MCT2 was the onlygene participating in an organized gene cluster enriched in K+dynamics. Indeed, theexpression of KATPsubunits, which mediate lactate increases with spiking activity, isspatially coupled to MCT2 distribution. Notably, MCT2 expression correlated withfluorodeoxyglucose positron emission tomography task-dependent glucose utilization.Finally, the MCT2 messenger RNA gradient closely overlaps with functional MRI brainregions associated with attention, arousal, and stress. Our results highlight neuronalMCT2 lactate transporter as a key component of the cross-talk between astrocytes andneurons and a link between metabolism, cortical structure, and state-dependent brain function.
Description
Keywords
ANLS, Brain metabolism, Gene expression, Monocarboxylate transporters, Cognition