Neuronal MCT2 promotes angiogenesis via lactate in the developing mouse neocortex

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.