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  • 1Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.

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Neural activity stimulates blood vessel growth in the developing brain. Monocarboxylate transporter 2 (MCT2) in neurons is key for this process, linking neural activity to metabolic adaptation and vascular development.

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Metabolism

Background:

  • Neural activity influences blood vessel (BV) formation and energy delivery in the developing brain to meet metabolic demands.
  • The precise mechanisms underlying this neurovascular coupling are not fully understood.

Purpose of the Study:

  • To investigate the role of monocarboxylate transporters in mediating neural activity-driven vascular development in the neonatal mouse neocortex.
  • To elucidate the molecular mechanisms linking neuronal activity, lactate metabolism, and angiogenesis.

Main Methods:

  • Neonatal mice underwent chronic whisker stimulation (WS) to induce neural activity.
  • Transcriptomic (RNA-seq) and spatial (RNA-scope) analyses were performed.
  • Functional experiments assessed the impact of neuronal MCT2 on angiogenic and metabolic responses.

Main Results:

  • Whisker stimulation upregulated monocarboxylate transporter 2 (MCT2) in neurons and MCT1 in endothelial cells (ECs).
  • These changes correlated with increased cortical lactate, elevated astrocytic vascular endothelial growth factor A (VEGFa), and enhanced angiogenesis.
  • Neuronal MCT2 was found to be essential for WS-induced angiogenic and metabolic adaptations, facilitating lactate flux and activating HIF1α and VEGFa signaling.

Conclusions:

  • Neuronal MCT2 plays a critical role in regulating lactate flux, signaling pathways, and vascular remodeling in the neonatal brain.
  • This study reveals a novel mechanism by which neural activity is linked to metabolic adaptation and vascular development.
  • Findings highlight the importance of lactate transport in neurovascular coupling during brain development.