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

Area of Science:

• Neuroscience
• Metabolic Neuroscience
• Molecular Neuroscience

Background:

• Brain energy metabolism relies on localized chemical energy generated by compartmentalized processes.
• Astrocyte-neuron lactate shuttle is crucial for energy transfer, involving specific membrane transporters.

Purpose of the Study:

• To characterize the spatial distribution of glucose and monocarboxylate membrane transporters in the human brain.
• To investigate the relationship between neuronal MCT2 transporter expression, cortical structure, and brain function.

Main Methods:

• Analysis of whole human brain gene expression data.
• Coexpression network analysis to identify gene clusters.
• Correlation analysis with cortical thickness, glucose utilization (FDG-PET), and functional MRI data.

Main Results:

• Neuronal MCT2 gene is enriched in the cerebral cortex, inversely correlated with cortical thickness.
• MCT2 expression is spatially coupled with potassium channel (K[Formula: see text]) subunit distribution, linked to lactate increases during neural activity.
• MCT2 expression correlates with task-dependent glucose utilization and overlaps with brain regions involved in attention, arousal, and stress.

Conclusions:

• Neuronal MCT2 lactate transporter is a key player in astrocyte-neuron metabolic coupling.
• MCT2 links brain metabolism, cortical structure, and state-dependent cognitive functions like attention and stress response.