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

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dc.article.numbere2204619119
dc.catalogadoryvc
dc.contributor.authorMedel Sierralta, Vicente Nicolas
dc.contributor.authorCrossley Karmelic, Nicolas Andrés
dc.contributor.authorGajardo, Ivana
dc.contributor.authorMuller, Eli
dc.contributor.authorBarros L., Felipe
dc.contributor.authorShine, James N.
dc.contributor.authorSierralta, Jimena
dc.date.accessioned2024-06-10T17:42:56Z
dc.date.available2024-06-10T17:42:56Z
dc.date.issued2022
dc.description.abstractBrain 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.
dc.description.funderInstituto de Neurociencia Biomédica
dc.description.funderNational Health and Medical Research Council
dc.description.funderFondo Nacional de Desarrollo Científico y Tecnológico
dc.description.funderAgencia Nacional de Investigación y Desarrollo
dc.fechaingreso.objetodigital2024-06-10
dc.fuente.origenScopus
dc.identifier.doi10.1073/pnas.2204619119
dc.identifier.eissn1091-16490
dc.identifier.issn1091-6490
dc.identifier.pubmedid35939682
dc.identifier.scopusidSCOPUS_ID:85135547036
dc.identifier.urihttps://doi.org/10.1073/pnas.2204619119
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/86673
dc.identifier.wosidWOS:000891284800010
dc.information.autorucEscuela de Medicina; Medel Sierralta, Vicente Nicolás; 0000-0003-2443-8683; 1049792
dc.information.autorucEscuela de Medicina; Crossley Karmelic, Nicolás Andrés; 0000-0002-3060-656X; 11224
dc.issue.numero33
dc.language.isoen
dc.nota.accesocontenido completo
dc.publisherNational Academy of Sciences
dc.publisherPNAS
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America
dc.revistaProceedings of the National Academy of Sciences of the United States of America
dc.rightsacceso abierto
dc.rights.licenseCC BY NC Attribution-NonCommercial-NonDerivs 4.0 International
dc.subjectANLS
dc.subjectBrain metabolism
dc.subjectGene expression
dc.subjectMonocarboxylate transporters
dc.subjectCognition
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods02 Zero hunger
dc.subject.odspa02 Hambre cero
dc.titleWhole-brain neuronal MCT2 lactate transporter expression links metabolism to human brain structure and function
dc.typeartículo
dc.volumen119
sipa.codpersvinculados1049792
sipa.codpersvinculados11224
sipa.trazabilidadSCOPUS;10-11-2022
sipa.trazabilidadORCID;2024-06-03
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