Serving as bridges between neurons and blood vessels in the brain, astrocytes (a type of glial cells) send specialized extensions or ‘endfeet’ around blood vessels to help shape these vessels during development and later control cerebral blood flow (CBF). Astrocytes belong to the ‘neurovascular unit’ (NVU), a multi-cellular ensemble serving as a hub for neurovascular interactions. Despite a wealth of knowledge on astrocytes, and while we know these cells become mature after birth, little is known about the mechanisms driving their recruitment around brain blood vessels, or about their contribution to blood vessel maturation.
In this study, Dr. Lacoste’s team addresses these knowledge gaps not only by thoroughly characterizing the time course of astrocyte-blood vessel interactions in the early postnatal mouse brain, but also by assessing gene expression changes in astrocytes during that period. Doing so, the researchers identify an important molecular player produced by astrocytes, namely HMGB1, which controls their morphology, their placement around blood vessels, and the maturation of NVU.
Using genetic tools to block the production of HMGB1 protein selectively in astrocytes early after birth, Dr. Lacoste’s team shows that HMGB1 controls astrocyte morphogenesis and the maturation of endfeet around blood vessels. Lack of HMGB1 in astrocytes at birth impaired blood vessel maturation and resulted in surprising alterations of behaviour in adult mice, that displayed an anxiety-like phenotype.
This study thus identifies a previously unknown mechanism controlling the interaction between astrocytes and blood vessels in the brain, helping scientists to better understand postnatal brain development and the contribution of non-neuronal cells to this process.
Publication: Freitas-Andrade, M., Comin, C.H., Van Dyken, P. et al. Astroglial Hmgb1 regulates postnatal astrocyte morphogenesis and cerebrovascular maturation. Nat Commun 14, 4965 (2023). https://doi.org/10.1038/s41467-023-40682-3