Whole-brain neuronal MCT2 lactate transporter expression links metabolism to human brain structure and function.
Vicente MedelNicolas A CrossleyIvana GajardoEli J MüllerLuis Felipe BarrosJames M ShineJimena SierraltaPublished in: Proceedings of the National Academy of Sciences of the United States of America (2022)
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[Formula: see text] dynamics. Indeed, the expression of K[Formula: see text] 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.
Keyphrases
- positron emission tomography
- cerebral ischemia
- network analysis
- poor prognosis
- computed tomography
- gene expression
- copy number
- genome wide
- white matter
- resting state
- subarachnoid hemorrhage
- dna methylation
- pet ct
- blood glucose
- spinal cord
- blood brain barrier
- adipose tissue
- brain injury
- big data
- working memory
- long non coding rna
- multiple sclerosis
- magnetic resonance
- optical coherence tomography
- pet imaging
- insulin resistance
- preterm infants
- electronic health record
- antibiotic resistance genes
- stress induced
- heat stress
- glycemic control