Neuronal MCT2 promotes angiogenesis via lactate in the developing mouse neocortex
Year: 2025
Type: article
Abstract: Neural activity drives blood vessel (BV) formation and energy substrate delivery in the developing brain to meet rising metabolic demands; however, the underlying mechanisms remain poorly understood. In this study, we exposed neonatal mice to chronic whisker stimulation (WS), a paradigm known to enhance BV formation in the somatosensory (S1) cortex. Transcriptomic (RNA-seq) and spatial (RNA-scope) analyses revealed that WS upregulated monocarboxylate transporter 2 (MCT2) in cortical neurons and MCT1 in endothelial cells (ECs). These changes coincided with increased cortical lactate levels, elevated astrocytic vascular endothelial growth factor A (VEGFa), and enhanced angiogenesis. Functional experiments demonstrated that neuronal MCT2 is essential for mediating WS-induced angiogenic and metabolic responses. Mechanistically, MCT2 facilitates L -lactate influx into the cortex with or without WS, promoting lactate uptake by neurons and astrocytes. This, in turn, induces MCT2 expression in neurons and activates hypoxia-inducible factor 1α (HIF1α) and VEGFa expression in astrocytes. Together, these findings uncover a previously unrecognized role for neuronal MCT2 in regulating lactate flux, signaling, and vascular remodeling, thereby linking neural activity to metabolic adaptation and vascular development in the neonatal mouse neocortex.
Source: Cell Death and Differentiation
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,790
Awards: G4051206502, G8368214014
OpenAlex ID: W4414817143