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Updated: Jul 16, 2026
Visualizing Synaptic Degeneration in Adult Drosophila in Association with Neurodegeneration
Published on: May 13, 2020
Visualization of degenerating axons in a dysmyelinating mouse mutant with axonal loss
Birgit Ey1, Igor Kobsar, Heinrich Blazyca
1Department of Neurology, Developmental Neurobiology, University of Wuerzburg, Josef-Schneiderstr. 11, D-97080 Wuerzburg, Germany.
Abstract:
Mice homozygously deficient for the myelin component P0 show loss of axons in peripheral nerves. In order to investigate the morphological characteristics of degenerating axons, we crossbred the myelin mutants with a transgenic mouse line expressing yellow fluorescent protein (YFP) in a small proportion of neurons. Peripheral nerves of the double mutants were prepared into small fiber bundles and investigated by fluorescence microscopy. We could identify the tips of degenerating axon as bulb-like structures. Additionally, by electron microscopy, these structures were characterized as axoplasmic extensions containing numerous membraneous compartments. By immunoelectron microscopy, the degenerating end bulbs were in contact with ensheathing Schwann cells that contained YFP-immunoreactivity possibly reflecting phagocytosis of axon material by these cells. Immunohistochemistry using antibodies against macrophages revealed that YFP-positive bulbs, but also other axonal swellings, were often associated with macrophages supporting our previous findings that myelin-related axonal loss is partially mediated by these cells.
Insights
Mice lacking the P0 myelin protein experience peripheral nerve axon loss. Degenerating axons form bulb-like structures, with Schwann cells and macrophages potentially clearing the damaged axon material.
Area of Science:
- Neuroscience
- Cell Biology
- Peripheral Nervous System Research
Background:
- The P0 protein is a critical component of peripheral nerve myelin.
- Deficiency in P0 leads to axonal degeneration in peripheral nerves.
- Understanding the morphology of degenerating axons is crucial for neurodegenerative disease research.
Purpose of the Study:
- To investigate the morphological characteristics of degenerating axons in P0-deficient mice.
- To elucidate the cellular mechanisms involved in myelin-related axonal loss.
- To identify the roles of Schwann cells and macrophages in clearing degenerating axonal material.
Main Methods:
- Crossbreeding P0-deficient mice with yellow fluorescent protein (YFP)-expressing transgenic mice.
- Fluorescence and electron microscopy of peripheral nerve fiber bundles.
- Immunoelectron microscopy and immunohistochemistry for cellular and molecular analysis.
Main Results:
- Degenerating axons in P0-deficient mice were identified as bulb-like structures.
- These bulbous structures were characterized as axoplasmic extensions with membranous compartments.
- Schwann cells and macrophages were observed in close proximity to degenerating axon bulbs, with evidence suggesting phagocytosis.
Conclusions:
- Myelin-related axonal loss involves the formation of distinct degenerating axon structures.
- Schwann cells and macrophages play a significant role in the clearance of degenerating axonal material in peripheral nerves.
- These findings contribute to understanding the pathogenesis of peripheral neuropathies associated with myelin defects.
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