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Absence of Wallerian Degeneration does not Hinder Regeneration in Peripheral Nerve
Abstract:
Wallerian degeneration of the distal stump of a severed peripheral nerve involves invasion by myelomonocytic cells, whose presence is necessary for destruction of myelin and for initiating mitosis in Schwann cells (Beuche and Friede, 1984). Degeneration of the distal ends of the axons themselves is assumed to occur by autolytic mechanisms. We describe a strain of mice (C57BL/6/Ola) in which leucocyte invasion is slow and sparse. In these mice, confirming Beuche and Friede, myelin removal is extremely slow. A new finding is that axon degeneration is also very slow. This is a consequence of lack of recruitment of myelomonocytic cells for if such recruitment is prevented in other mouse strains by a monoclonal antibody against the complement type 3 receptor (Rosen and Gordon, 1987) axon degeneration is again slowed. We have also, surprisingly, found that nerve regeneration in the C57BL/6/Ola mice is not impeded by the presence of largely intact axons in the distal stump and absence of recruited cells, myelin debris and the absence of Schwann cell mitosis.
Insights
Peripheral nerve injury repair is slowed when immune cells are absent, impacting myelin and axon breakdown. Surprisingly, nerve regeneration proceeds effectively even with delayed degeneration.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Wallerian degeneration is crucial for peripheral nerve repair, involving immune cell-mediated myelin breakdown and Schwann cell proliferation.
- Axon degeneration is typically considered an autolytic process following nerve injury.
Purpose of the Study:
- To investigate the role of myelomonocytic cells in Wallerian degeneration and nerve regeneration.
- To characterize nerve degeneration and regeneration in a mouse strain with impaired leukocyte invasion (C57BL/6/Ola).
Main Methods:
- Utilized a C57BL/6/Ola mouse strain with naturally slow leukocyte invasion.
- Administered a monoclonal antibody against the complement type 3 receptor to inhibit myelomonocytic cell recruitment in other mouse strains.
- Observed and quantified myelin and axon degeneration, Schwann cell mitosis, and nerve regeneration.
Main Results:
- In C57BL/6/Ola mice, both myelin and axon degeneration were significantly delayed due to sparse myelomonocytic cell invasion.
- Inhibiting myelomonocytic cell recruitment in other strains also slowed axon degeneration.
- Nerve regeneration in C57BL/6/Ola mice was not hindered by the presence of intact axons and reduced debris.
Conclusions:
- Myelomonocytic cell recruitment is essential for efficient Wallerian degeneration of both myelin and axons.
- Efficient Wallerian degeneration is not a prerequisite for effective peripheral nerve regeneration.
- This challenges the traditional understanding of nerve repair mechanisms.