Decreased microglial Wnt/β-catenin signalling drives microglial pro-inflammatory activation in the developing brain.

ABSTRACT: Microglia of the developing brain have unique functional properties but how their activation states are regulated is poorly understood. Inflammatory activation of microglia in the still-developing brain of preterm-born infants is associated with permanent neurological sequelae in 9 million infants every year. Investigating the regulators of microglial activation in the developing brain across models of neuroinflammation-mediated injury (mouse, zebrafish) and primary human and mouse microglia we found using analysis of genes and proteins that a reduction in Wnt/β-catenin signalling is necessary and sufficient to drive a microglial phenotype causing hypomyelination. We validated in a cohort of preterm-born infants that genomic variation in the Wnt pathway is associated with the levels of con

SUBMITTER: Van Steenwinckel J 

PROVIDER: S-EPMC6906599 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature