Whole-brain neuronal MCT2 lactate transporter expression links metabolism to human brain structure and function

Vicente Medel, Nicolás Crossley, Ivana Gajardo, Eli Muller, L. Felipe Barros, James M. Shine, Jimena Sierralta

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Brain activity is constrained by local availability of chemical energy, which is generated through compartmentalized metabolic processes. By analyzing data of whole human brain gene expression, we characterize the spatial distribution of seven glucose and monocarboxylate membrane transporters that mediate astrocyte–neuron lactate shuttle transfer of energy. We found that the gene coding for neuronal MCT2 is the only gene enriched in cerebral cortex where its abundance is inversely correlated with cortical thickness. Coexpression network analysis revealed that MCT2 was the only gene participating in an organized gene cluster enriched in K+ dynamics. Indeed, the expression of KATP subunits, which mediate lactate increases with spiking activity, is spatially coupled to MCT2 distribution. Notably, MCT2 expression correlated with fluorodeoxyglucose positron emission tomography task-dependent glucose utilization. Finally, the MCT2 messenger RNA gradient closely overlaps with functional MRI brain regions associated with attention, arousal, and stress. Our results highlight neuronal MCT2 lactate transporter as a key component of the cross-talk between astrocytes and neurons and a link between metabolism, cortical structure, and state-dependent brain function.

Original languageEnglish
Article numbere2204619119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number33
DOIs
StatePublished - 16 Aug 2022
Externally publishedYes

Keywords

  • ANLS
  • brain metabolism
  • cognition
  • gene expression
  • monocarboxylate transporters

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