Glycogen synthase kinase-3 β inhibition enhances myelination in preterm newborns with intraventricular hemorrhage, but not recombinant Wnt3A.

Glycogen synthase kinase-3β inhibition enhances myelination in preterm newborns with intraventricular hemorrhage, but not recombinant Wnt3A.
Neurobiol Dis. 2018 Jun 22;:
Authors: Dohare P, Cheng B, Ahmed E, Yadala V, Singla P, Thomas S, Kayton R, Ungvari Z, Ballabh P
Abstract
Intraventricular hemorrhage (IVH) in preterm infants results in reduced proliferation and maturation of oligodendrocyte progenitor cells (OPCs), and survivors exhibit reduced myelination and neurological deficits. Wnt signaling regulates OPC maturation and myelination in a context dependent manner. Herein, we hypothesized that the occurrence of IVH would downregulate Wnt signaling, and that activating Wnt signaling by GSK-3β inhibition or Wnt3A recombinant human protein (rh-Wnt3A) treatment might promote maturation of OPCs, myelination of the white matter, and neurological recovery in premature rabbits with IVH. These hypotheses were tested in autopsy samples from preterm infants and in a rabbit model of IVH. Induction of IVH reduced expressions of activated β-catenin, TCF-4, and Axin2 transcription factors in preterm newborns. Both AR-A014418 (ARA) and Wnt-3A treatment activated Wnt signaling. GSK-3β inhibition by intramuscular ARA treatment accelerated maturation of OPCs, myelination, and neurological recovery in preterm rabbits with IVH compared to vehicle controls. In contrast, intracerebroventricular rh-Wnt3A treatment failed to enhance myelination and ...

Source: Neurobiology of Disease - June 22, 2018 Category: Neurology Authors: Dohare P, Cheng B, Ahmed E, Yadala V, Singla P, Thomas S, Kayton R, Ungvari Z, Ballabh P Tags: Neurobiol Dis Source Type: research