# Myelin sheaths persist for weeks following axon degeneration

## TL;DR

Myelin sheaths remain intact for weeks after axon degeneration and show limited interaction with microglia.

## Contribution

The study reveals that myelin sheaths persist after axon loss and that microglia rarely respond to injured axons or myelin.

## Key findings

- Myelin sheaths without axons can persist for weeks and gradually shrink.
- Microglia rarely engage with injured axons or de-axoned myelin sheaths.
- Myelinated axons delay debris clearance after injury.

## Abstract

Axon degeneration underlies clinical deficits in traumatic injuries and neurodegenerative disease. It is not clear how myelinating oligodendrocytes are directly affected by or respond to axon injury and loss. Here, we combined intravital imaging with laser axotomy or single neuron ablation to determine the longitudinal responses by oligodendrocytes that myelinate the degenerating axon. We find that while axons rapidly degenerate, myelin sheaths devoid of axon can persist for weeks. These remaining myelin sheaths lose compaction and slowly shrink. Local to the injury, oligodendrocyte homeostasis is largely maintained, with only a brief change in myelin sheath structural plasticity. After neuron ablation and axotomy, clearance of axon debris is delayed if the axon is myelinated. However, longitudinal imaging of microglia revealed only rare microglial engagement with injured axons, regardless of myelination status. Likewise, microglia did not engage with de-axoned myelin sheaths. These findings highlight the stability of myelinating oligodendrocytes and provide insight into homeostatic neuroglia responses following injury.

Axon degeneration results in persistent, empty myelin sheaths and elicits unexpectedly rare phagocytic responses from microglia.