Visual experience-driven switch in endothelial metabolic transporters is essential for cerebrovascular maturation
Authors: N. Kim, E.-Y. Choi, S. Chae, J.-Y. Jeong, H. K. Kim, W.-J. Oh
Abstract
Angiogenesis and blood-brain barrier (BBB) maturation are tightly regulated by coordinated interactions among neuronal, glial, and endothelial cells. Although neuronal activity is essential for postnatal cerebrovascular development, how it is translated into endothelial programs that coordinate vascular maturation remains unknown. Here, we show that visual experience drives metabolic reprogramming in brain endothelial cells by decreasing the lactate transporter MCT1 while increasing the glucose transporter GLUT1, a switch that is essential for proper vascular development. Sustained endothelial expression of MCT1 impaired vascular development and BBB maturation, resulting in vascular leakage. Mechanistically, the developmental decline in TGF-beta signaling drives the endothelial MCT1-to-GLUT1 transition. Endothelial-derived TGF-beta1 further reinforces the immature angiogenic state through a lactate-dependent autocrine positive feedback loop, whereas sensory experience promotes astrocyte maturation, which attenuates endothelial TGF-beta signaling, potentially by altering the perivascular environment. Together, our findings identify a neuron-astrocyte-endothelial metabolic signaling axis that links sensory experience to endothelial metabolic reprogramming and coordinates the transition from angiogenesis to BBB maturation.
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The zebrafish study examines endothelial Notch signals coordinating pericyte development with vascular growth, rather than sensory experience-driven endothelial metabolic switching.
Abstract
Pericyte specification and expansion must be coordinated with vascular growth to establish a functional cerebrovascular network, yet how endothelial signals control these distinct developmental transitions remains incompletely understood. Here, using genetic manipulation, single-cell transcriptomic analysis, and longitudinal in vivo imaging in zebrafish, we identify ligand-specific endothelial Notch signaling as a mechanism coordinating brain pericyte development. Endothelial Jag2b is required for efficient pericyte specification from pericerebral progenitor pools and subsequently promotes Notch-dependent pericyte proliferation and population expansion. By contrast, endothelial Dll4 restrain…
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EXPRESS: Targeting the Neurovascular Interface: Endothelial Optogenetics as a New Frontier for Brain Circuit Interrogation.Shu-Min Gong, Ye Liao, Jia-Le Ye et al. · 2026 · Journal of Cerebral Blood Flow and Metabolism · Not summarized yet
This perspective discusses optogenetic manipulation of brain endothelium, while the paper studies sensory activity shaping endothelial metabolism and cerebrovascular maturation.
Abstract
The advent of optogenetics has revolutionized neuroscience by enabling precise manipulation of neural circuits, solidifying a neuron-centric view of brain function. This perspective has increasingly expanded to encompass non-neuronal cells, with the optogenetic control of astrocytes, microglia, and pericytes revealing their active roles in information processing. Yet the vascular endothelium long regarded as a passive conduit has remained largely unexplored through this lens. Here we discuss the emerging field of endothelial optogenetics, which seeks to isolate the cell-autonomous signaling capacity of brain endothelial cells, distinct from their hemodynamic functions. We explore the hypothe…
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The study investigates astrocyte signaling during sensory-evoked blood-volume changes, whereas the paper examines sensory experience and astrocyte effects on endothelial maturation.
Abstract
ABSTRACT Astrocytes are recognized as key components of neurovascular coupling (NVC), yet whether and how astrocytic engagement in NVC depends on sensory stimulus duration remains unclear. Here, we investigated a duration‐dependent astrocytic mechanism underlying cerebral blood volume (CBV) modulation by comparing neurovascular responses to brief (5 s) and prolonged (20 s) sensory stimulation, using in vivo intrinsic optical signal (IOS) imaging and two‐photon microscopy combined with electrophysiology and vascular cannulation. We show that prolonged stimulation selectively recruits an integrated astrocytic signaling cascade involving aquaporin‐4 (AQP4)‐mediated volume changes, Ca2+ influx t…
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This study characterizes pericyte and capillary changes in diabetic mice, rather than developmental endothelial transporter changes and blood–brain barrier maturation.
Abstract
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Abstract
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This narrative review covers brain endothelial functions and their links to psychiatric disorders, whereas the paper tests developmental metabolic regulation.
Abstract
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Thyroid hormones and neurovascular development: An integrated framework.I. Ochando, D. Navarro · 2026 · Frontiers in neuroendocrinology (Print) · Not summarized yet
This framework reviews thyroid hormone regulation of neurovascular development, while the paper investigates sensory experience-dependent endothelial transporter switching.
Abstract
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Endothelial Malat1 promotes post-stroke angiogenesis and neurovascular recovery via the Tek axis.Tian-Qing Xiong, Meng-Qi Zhang, Ping Sun et al. · 2026 · Brain : a journal of neurology · Not summarized yet
The study links endothelial Malat1 to angiogenesis and recovery after stroke, rather than to sensory experience-driven vascular maturation.
Abstract
Ischemic stroke remains a leading cause of mortality and disability worldwide, yet current therapeutic strategies, such as thrombolysis and thrombectomy, are constrained by narrow treatment windows and incomplete microvascular repair. While angiogenesis is pivotal for long-term functional recovery, the epigenetic mechanisms governing post-stroke vascular remodeling remain poorly understood. Here, we demonstrate that the long non-coding RNA (lncRNA) Malat1 acts as a critical endothelial regulator of angiogenesis and neurological restoration. Using an endothelium-specific Malat1 overexpression mouse model (EC-Malat1 Tg), we demonstrate endothelial Malat1 upregulation enhances angiogenesis, res…
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