Related Experiment Video
Updated: Jun 25, 2026
Morphological and Functional Evaluation of Axons and their Synapses during Axon Death in Drosophila melanogaster
Published on: March 16, 2020
Deficiency of the complement regulator CD59a exacerbates Wallerian degeneration
Valeria Ramaglia1, Rosalind Helen Mary King, Bryan Paul Morgan
1Neurogenetics Laboratory, University of Amsterdam, Amsterdam, The Netherlands.
Insights
CD59a deficiency exacerbates Wallerian degeneration (WD) by increasing membrane attack complex (MAC) deposition and axonal damage after nerve injury. This highlights MAC
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- The complement system, particularly the membrane attack complex (MAC), plays a role in Wallerian degeneration (WD) after nerve injury.
- Previous research demonstrated MAC's involvement in rapid axonal degradation and myelin clearance during WD.
Purpose of the Study:
- To investigate the role of CD59a, a negative regulator of MAC, in the process of Wallerian degeneration.
- To determine how CD59a deficiency impacts MAC deposition and axonal integrity during WD.
Main Methods:
- Utilizing CD59a-deficient mice and wildtype controls following peripheral nerve injury.
- Quantifying MAC deposition levels and residual axonal content.
- Assessing endoneurial macrophage infiltration at the injury site.
Main Results:
- CD59a-deficient mice exhibited higher MAC deposition compared to wildtype controls.
- Axonal content was significantly lower in CD59a-deficient mice, indicating increased axonal damage.
- Endoneurial macrophage numbers were elevated in CD59a-deficient mice one day post-injury.
Conclusions:
- CD59a deficiency exacerbates Wallerian degeneration by enhancing MAC-mediated axonal damage.
- MAC deposition is a critical determinant of axonal loss in WD.
- These findings contribute to understanding axon loss mechanisms in nerve injury and disease.
Abstract:
The complement system is implicated in Wallerian degeneration (WD). We have previously shown that the membrane attack complex (MAC), the terminal activation product of the complement cascade, mediates rapid axonal degradation and myelin clearance during WD after peripheral nerve injury. In this study we analyzed the contribution of CD59a, a cell membrane negative regulator of the MAC, to WD. Following injury, the level of MAC deposition was higher in the CD59a deficient mice than wildtypes whereas the residual axonal content was lower in CD59a deficient mice than wildtypes, strongly implicating MAC as a determinant of axonal damage during WD. The number of endoneurial macrophages was significantly higher in CD59a deficient mice compared to wildtypes at 1 day post-injury. These findings are relevant to the understanding of the mechanisms of axon loss in injury and disease.
