Sirt2 promotes white matter oligodendrogenesis during development and in models of neonatal hypoxia

Beata Jablonska (), Katrina L. Adams, Panagiotis Kratimenos, Zhen Li, Emma Strickland, Tarik F. Haydar, Katharina Kusch, Klaus-Armin Nave and Vittorio Gallo ()
Additional contact information
Beata Jablonska: Children’s National Hospital
Katrina L. Adams: Children’s National Hospital
Panagiotis Kratimenos: Children’s National Hospital
Zhen Li: Children’s National Hospital
Emma Strickland: Children’s National Hospital
Tarik F. Haydar: Children’s National Hospital
Katharina Kusch: Max Planck Institute of Experimental Medicine, Department of Neurogenetics
Klaus-Armin Nave: Max Planck Institute of Experimental Medicine, Department of Neurogenetics
Vittorio Gallo: Children’s National Hospital

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: Abstract Delayed oligodendrocyte (OL) maturation caused by hypoxia (Hx)-induced neonatal brain injury results in hypomyelination and leads to neurological disabilities. Previously, we characterized Sirt1 as a crucial regulator of OL progenitor cell (OPC) proliferation in response to Hx. We now identify Sirt2 as a critical promoter of OL differentiation during both normal white matter development and in a mouse model of Hx. Importantly, we find that Hx reduces Sirt2 expression in mature OLs and that Sirt2 overexpression in OPCs restores mature OL populations. Reduced numbers of Sirt2+ OLs were also observed in the white matter of preterm human infants. We show that Sirt2 interacts with p27Kip1/FoxO1, p21Cip1/Cdk4, and Cdk5 pathways, and that these interactions are altered by Hx. Furthermore, Hx induces nuclear translocation of Sirt2 in OPCs where it binds several genomic targets. Overall, these results indicate that a balance of Sirt1 and Sirt2 activity is required for developmental oligodendrogenesis, and that these proteins represent potential targets for promoting repair following white matter injury.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-32462-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32462-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-32462-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().