Language

English

Publication Date

8-8-2025

Journal

Nature Communications

DOI

10.1038/s41467-025-61841-8

PMID

40781224

PMCID

PMC12334574

PubMedCentral® Posted Date

8-8-2025

PubMedCentral® Full Text Version

Post-print

Abstract

The blood-brain barrier (BBB), formed by specialized endothelial cells (ECs), regulates the extracellular composition of the central nervous system (CNS). Little is known about whether there are regional specializations of the BBB that may control the function of specific neural circuits. We use single cell RNA-seq to characterize ECs from nine CNS regions in male mice: cortex, hippocampus, cerebellum, spinal cord, striatum, thalamus, hypothalamus, midbrain, and medulla/pons. Although there is a core BBB transcriptional profile, there are significant regional specializations. Stra6, a retinoid transporter, is highly enriched in the BBB of the nucleus accumbens shell (ShNAc) and ventral cochlear nucleus, and is controlled by dietary vitamin A, through endothelial RARƔ. EC Stra6 regulates the deposition of retinoids specifically in the ShNAc and cochlear nucleus, and is required for the function of the ShNAc, in a retinoid-dependent manner. Thus regional specializations of the BBB can regulate the function of local brain regions.

Keywords

Animals, Blood-Brain Barrier, Male, Mice, Endothelial Cells, Vitamin A, Membrane Proteins, Mice, Inbred C57BL, Nucleus Accumbens, Retinoids, Brain, Receptors, Retinoic Acid, Single-Cell Analysis, Blood-brain barrier, Neuro-vascular interactions

Published Open-Access

yes

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