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

Area of Science:

• Neuroscience
• Cell Biology
• Immunology

Background:

• Microglia clear myelin debris, essential for remyelination and preventing neurological decline in aging and multiple sclerosis (MS).
• The molecular mechanisms controlling microglial expansion and function during remyelination are not fully understood.

Purpose of the Study:

• To investigate the role of mitotic kinase Aurora B kinase (Aurkb) in microglial development, homeostasis, and remyelination processes.

Main Methods:

• Neonatal and inducible adult deletion of Aurkb in mice.
• Analysis of microglial morphology, proliferation, and mitosis.
• Assessment of microglial activation via LPS stimulation.
• Evaluation of remyelination and myelin debris clearance in a cuprizone (CPZ)-induced demyelination model.

Main Results:

• Aurkb upregulation was observed in microglia during development and in MS models.
• Aurkb deletion disrupted microglial proliferation, morphology, and homeostasis, leading to mitotic defects.
• Aurkb deficiency impaired microglial response to inflammation and compromised myelin debris clearance.
• Aurkb-deficient mice showed reduced remyelination and oligodendrocyte regeneration in the CPZ model, linked to diminished autophagy.

Conclusions:

• Aurora B kinase (Aurkb) is a critical regulator of microglial development, maintenance, and response to demyelination.
• Aurkb is essential for effective myelin debris clearance and subsequent remyelination, independent of microglial cell number.
• Targeting Aurkb may offer therapeutic strategies for neurological disorders involving impaired remyelination.