# Aurkb deficiency disrupts microglial development, homeostasis and hinders remyelination following cuprizone-induced demyelination

## TL;DR

Aurkb is essential for microglial development and function, and its deficiency impairs the clearance of myelin debris and remyelination in disease models.

## Contribution

This study identifies Aurkb as a novel regulator of microglial development, homeostasis, and remyelination.

## Key findings

- Aurkb deficiency disrupts microglial mitosis, density, and morphology in neonatal mice.
- Aurkb loss in adulthood leads to microglial dystrophy and impaired autophagy.
- Aurkb-deficient microglia fail to clear myelin debris and hinder remyelination in demyelination models.

## Abstract

Microglia are crucial for phagocytic clearance of myelin debris, which hinders remyelination and leads to neurological decline during aging and in multiple sclerosis (MS). However, the molecular mechanism enabling microglia to expand and function effectively in remyelination remains elusive. Here, we identified that mitotic kinase Aurkb was upregulated in microglia during early development and in MS. Neonatal deletion of Aurkb disrupted cell density, morphology, and proliferation, which is attributed to stalled mitosis. Inducible Aurkb ablation in adulthood led to microglial dystrophy and disrupted homeostasis. Aurkb deficiency compromised microglial activation in response to LPS-induced inflammation. Critically, Aurkb-deficient mice exhibited accumulated myelin debris and impaired oligodendrocyte regeneration and remyelination in the CPZ-induced demyelination model. Additionally, Aurkb deletion inhibited microglial clearance of myelin debris, independent of reduced microglia numbers. This defect was associated with diminished autophagy. Together, these findings establish Aurkb as a key regulator of microglial development, homeostasis, and responses to remyelination.

•Aurkb increases in a subset of microglia during early development and demyelination•Neonatal Aurkb ablation impairs microglial mitosis, density, and morphology•Aurkb loss in adulthood disrupts microglial homeostasis, activation, and autophagy•Aurkb deficiency limits microglial phagocytic function and hinders remyelination

Aurkb increases in a subset of microglia during early development and demyelination

Neonatal Aurkb ablation impairs microglial mitosis, density, and morphology

Aurkb loss in adulthood disrupts microglial homeostasis, activation, and autophagy

Aurkb deficiency limits microglial phagocytic function and hinders remyelination

Neuroscience; Cell biology