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Calcium-mediated degeneration of the axonal cytoskeleton in the Ola mouse
J D Glass1, B L Schryer, J W Griffin
1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-6965.
Abstract:
The C57BL/Ola (Ola) mouse is a mutant substrain in which transected axons undergo very slow Wallerian degeneration. Because axonal degradation during Wallerian degeneration is calcium dependent, we tested whether Ola axons are susceptible to calcium-mediated axonal degeneration by comparing neurofilament degradation between Ola and C57BL/6 mice in sciatic nerve explants. Using immunoblot analysis of neurofilament degradation and electron microscopy we found that as in normal axons, axonal degeneration in the Ola is calcium dependent. However, when compared with normal animals, higher levels of calcium were required for complete degradation of neurofilaments in Ola nerve, suggesting a relative insensitivity to calcium-mediated degeneration in the Ola. We conclude that calcium-activated proteases are present and active in Ola axons but that higher levels of calcium are required to accomplish complete axonal degradation. These results suggest a possible mechanism for prolonged survival of transected Ola axons and provide potential insight into the pathophysiology of axonal degeneration in injury and disease.
Insights
The C57BL/Ola mouse exhibits slow Wallerian degeneration due to a relative insensitivity to calcium-mediated axonal breakdown. Higher calcium levels are needed for neurofilament degradation in Ola axons compared to normal C57BL/6 mice.
Area of Science:
- Neuroscience
- Cell Biology
- Genetics
Background:
- Wallerian degeneration is a calcium-dependent process crucial for clearing damaged axons.
- The C57BL/Ola mouse substrain shows significantly delayed Wallerian degeneration after axonal injury.
Purpose of the Study:
- To investigate the role of calcium sensitivity in the delayed Wallerian degeneration observed in C57BL/Ola mouse axons.
- To compare the calcium-mediated neurofilament degradation between Ola and C57BL/6 mouse sciatic nerve explants.
Main Methods:
- Sciatic nerve explant cultures from C57BL/Ola and C57BL/6 mice.
- Immunoblot analysis to quantify neurofilament degradation.
- Electron microscopy to assess axonal integrity.
Main Results:
- Axonal degeneration in Ola mice is calcium-dependent, similar to normal mice.
- However, Ola axons require significantly higher calcium concentrations for complete neurofilament degradation.
- This indicates a relative insensitivity to calcium-mediated degeneration in the Ola substrain.
Conclusions:
- Calcium-activated proteases are present and active in Ola axons, but their function is modulated.
- The findings suggest that altered calcium sensitivity is a key mechanism underlying the prolonged survival of transected Ola axons.
- This research offers insights into axonal degeneration in neurological injury and disease.