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Astroglial Hmgb1 regulates postnatal astrocyte morphogenesis and cerebrovascular maturation

Moises Freitas-Andrade, Cesar H. Comin (ORCID), Peter Van Dyken, Julie Ouellette, Joanna Raman-Nair, Nicole Blakeley, Qing Yan Liu, Sonia Leclerc, Youlian Pan, Ziying Liu, Micaël Carrier, Karan Thakur, Alexandre Savard, Gareth M. Rurak, Marie-Ève Tremblay, Natalina Salmaso, Luciano Da F. Costa, Gianfilippo Coppola, Baptiste Lacoste

Nature Communications, 14(1): 4965. . DOI: 10.1038/s41467-023-40682-3.

Abstract

Astrocytes are intimately linked with brain blood vessels, an essential relationship for neuronal function. However, astroglial factors driving these physical and functional associations during postnatal brain development have yet to be identified. By characterizing structural and transcriptional changes in mouse cortical astrocytes during the first two postnatal weeks, we find that high-mobility group box 1 ( Hmgb1 ), normally upregulated with injury and involved in adult cerebrovascular repair, is highly expressed in astrocytes at birth and then decreases rapidly. Astrocyte-selective ablation of Hmgb1 at birth affects astrocyte morphology and endfoot placement, alters distribution of endfoot proteins connexin43 and aquaporin-4, induces transcriptional changes in astrocytes related to cytoskeleton remodeling, and profoundly disrupts endothelial ultrastructure. While lack of astroglial Hmgb1 does not affect the blood-brain barrier or angiogenesis postnatally, it impairs neurovascular coupling and behavior in adult mice. These findings identify astroglial Hmgb1 as an important player in postnatal gliovascular maturation.

Citation

@article{Freitas-Andrade2023Astroglial,
  title   = {Astroglial Hmgb1 regulates postnatal astrocyte morphogenesis and cerebrovascular maturation},
  author  = {Freitas-Andrade, Moises and Comin, Cesar H. and Van Dyken, Peter and Ouellette, Julie and Raman-Nair, Joanna and Blakeley, Nicole and Liu, Qing Yan and Leclerc, Sonia and Pan, Youlian and Liu, Ziying and Carrier, Micaël and Thakur, Karan and Savard, Alexandre and Rurak, Gareth M. and Tremblay, Marie-Ève and Salmaso, Natalina and Da F. Costa, Luciano and Coppola, Gianfilippo and Lacoste, Baptiste},
  journal = {Nature Communications},
  year    = {2023},
  volume  = {14},
  number  = {1},
  pages   = {4965},
  doi     = {10.1038/s41467-023-40682-3}
}