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

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 p27^Kip1/FoxO1, p21^Cip1/Cdk4, and Cdk5 pathways, and that these interactions are al

SUBMITTER: Jablonska B 

PROVIDER: S-EPMC9378658 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature