Astroglial Hmgb1 regulates postnatal astrocyte morphogenesis and cerebrovascular maturation

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dc.contributor.authorFreitas-Andrade, Moises
dc.contributor.authorComin, Cesar H.
dc.contributor.authorVan Dyken, Peter
dc.contributor.authorOuellette, Julie
dc.contributor.authorRaman-Nair, Joanna
dc.contributor.authorBlakeley, Nicole
dc.contributor.authorLiu, Qing Yan
dc.contributor.authorLeclerc, Sonia
dc.contributor.authorPan, Youlian
dc.contributor.authorLiu, Ziying
dc.contributor.authorCarrier, Micaël
dc.contributor.authorThakur, Karan
dc.contributor.authorSavard, Alexandre
dc.contributor.authorRurak, Gareth M.
dc.contributor.authorTremblay, Marie-Ève
dc.contributor.authorSalmaso, Natalina
dc.contributor.authorda F. Costa, Luciano
dc.contributor.authorCoppola, Gianfilippo
dc.contributor.authorLacoste, Baptiste
dc.date.accessioned2024-01-25T22:50:45Z
dc.date.available2024-01-25T22:50:45Z
dc.date.copyright2023en_US
dc.date.issued2023
dc.descriptionWe thank Drs. Simon Chen and Chenghua Gu for their valuable comments on the manuscript; the histology services provided by the Louise Pelletier Histopathology Core Facility at the University of Ottawa; the animal care and veterinary services at the University of Ottawa; and Jinjing Gong, Katie Barret, Colleen Urban, Elizabeth Mahoney and Seth Meyers (NanoString Technologies, Inc.) for coordinating spatial transcriptomics experiments. We would also like to thank Cédric Gravel for help with immunostaining work.en_US
dc.description.abstractAstrocytes 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.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipFor this work, B.L. was supported by research grants from the Canadian Institutes of Health Research (grant #388805) and the Natural Sciences and Engineering Council of Canada (grant RGPIN-2018-04456). M-E.T. was supported by grants from the Natural Sciences and Engineering Council of Canada (grant RGPIN- 2014-05308) and a Tier 2 Canada Research Chair in Neurobiology of Aging and Cognition. M.C. was supported by a Doctoral Scholarship from the Fonds de recherche du Québec. C.H.C. thanks FAPESP (grant #2021/12354-8). L.daF.C. thanks CNPq (grant #307085/2018-0) and FAPESP (grant #2015/22308-2).en_US
dc.identifier.citationFreitas-Andrade, M., Comin, C. H., Van Dyken, P., Ouellette, J., Raman-Nair, J., Blakeley, N., ... Lacoste, Baptiste. (2023). Astroglial Hmgb1 regulates postnatal astrocyte morphogenesis and cerebrovascular maturation. Nature Communications, 14, 4965. https://doi.org/10.1038/s41467-023-40682-3en_US
dc.identifier.urihttps://doi.org/10.1038/s41467-023-40682-3
dc.identifier.urihttp://hdl.handle.net/1828/15894
dc.language.isoenen_US
dc.publisherNature Communicationsen_US
dc.subject.departmentDivision of Medical Sciences
dc.subject.departmentSchool of Medical Sciences
dc.titleAstroglial Hmgb1 regulates postnatal astrocyte morphogenesis and cerebrovascular maturationen_US
dc.typeArticleen_US

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