Natural light experience induces metabolic switch that promotes cerebrovascular maturation

초록

Early light exposure is a key environmental factor that accelerates brain development in mice. When their eyes open around postnatal day 14 (P14), light A triggers molecular and structural changes in the brain. These changes affect 40 neuronal activity, influencing angiogenesis, blood flow, and blood-brain barrier 30 (BBB) function. The vascular responses to these changes are complex and depend on various factors, including the specific neurons activated, the brain region involved, and the age of the animal. However, much less is known about the underlying molecular mechanism in brain endothelial cells (BECs) following sensory experience during development. In this study, we employed translatome analysis with the RiboTag method to compare BECs at P10 and P30, before and after eye opening, and identified 32 genes that respond specifically to light, through a parallel comparison with a previously reported database. We confirmed that light exposure induces developmental changes in the expression of light-responsive genes, with these changes completely abolished in dark-reared mice. Among these genes, the expression of monocarboxylate transporter 1 (MCT1), a lactate transporter, showed a significant decrease in response to light, whereas glucose transporter 1 (GLUT1) expression increased. Under dark-reared conditions, this metabolic shift was abolished, accompanied by vascular leakage and immature astrocytes in the visual cortex. Moreover, we found that the activation of TGF-β signaling played a role in the reciprocal switch of both metabolic transporters in BECs. In conclusion, the neuronal activation may suppress TGF-β signaling, possibly via astrocytes, thereby modulating the balance of lactate and glucose metabolism through the regulation of MCT1 and GLUT1 expression in BECs. This process ultimately contributes to vascular maturation, including the BBB formation.