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Comparison of matrix metalloproteinase expression during Wallerian degeneration in the central and peripheral nervous systems

Hughes, P.M., Wells, G.M.A., Perry, V.H., Brown, M.C. and Miller, K.M. (2002) Comparison of matrix metalloproteinase expression during Wallerian degeneration in the central and peripheral nervous systems Neuroscience, 113, (2), pp. 273-287. (doi:10.1016/S0306-4522(02)00183-5).

Record type: Article

Abstract

The matrix metalloproteinases (MMPs) are a large family of zinc-dependent enzymes which are able to degrade the protein components of the extracellular matrix. They can be placed into subgroups based on structural similarities and substrate specificity. Aberrant expression of these destructive enzymes has been implicated in the pathogenesis of immune-mediated neuroinflammatory disorders. In this study we investigate the involvement of MMPs, from each subgroup, in Wallerian degeneration in both the central and peripheral nervous systems.
Wallerian degeneration describes the process initiated by transection of a nerve fibre and entails the degradation and removal of the axon and myelin from the distal stump. A similar degenerative process occurs as the final shared pathway contributing to most common neuropathies. MMP expression and localisation in the peripheral nervous system are compared with events in the CNS during Wallerian degeneration. Within 3 days after axotomy in the peripheral nervous system, MMP-9, MMP-7 and MMP-12 are elevated. These MMPs are produced by Schwann cells, endothelial cells and macrophages. The temporospatial expression of activated MMP-9 correlates with breakdown of the blood-nerve barrier.
In the CNS, 1 week after optic nerve crush, four MMPs are induced and primarily localised to astrocytes, not microglia or oligodendrocytes. In the degenerating optic nerve, examined at later time points (4, 8, 12 and 18 weeks), MMP expression was down-regulated. The absence of MMPs in oligodendrocytes and mononuclear phagocytes during Wallerian degeneration may contribute to the slower removal of myelin debris observed in the CNS. The low level of the inactive pro-form of MMP-9 in the degenerating optic nerve may explain why the blood-brain barrier remains intact, while the blood-nerve barrier is rapidly broken down.
We conclude that the difference in the level of expression, activation state and cellular distribution of MMPs may contribute to the different sequence of events observed during Wallerian degeneration in the peripheral compared to the CNS.

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More information

Submitted date: 29 October 2001
Published date: 1 January 2002
Keywords: MMP-9, MMP-3, Schwann cells, blood-nerve barrier, proteinases and astrocytes

Identifiers

Local EPrints ID: 56291
URI: http://eprints.soton.ac.uk/id/eprint/56291
ISSN: 0306-4522
PURE UUID: 95fcad0c-316f-44ed-a50e-07f0456c239a

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Date deposited: 08 Aug 2008
Last modified: 17 Jul 2017 14:31

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Contributors

Author: P.M. Hughes
Author: G.M.A. Wells
Author: V.H. Perry
Author: M.C. Brown
Author: K.M. Miller

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