Abstract
The mechanisms that trigger Wallerian degeneration (WD) of peripheral nerves after injury are not well understood. During the early period of WD, fragmentation of myelin into ovoid structures occurs near the Schmidt-Lantermann incisures (SLI), a noncompact region of the myelin sheath containing autotypical adherens junction. In this study, we found that new filamentous actin polymerization occurs in the SLI of mouse sciatic nerves after injury and that its inhibition prevented not only the degradation of E-cadherin in the SLI but also myelin ovoid formation. However, the inhibition of actin polymerization could not block Schwann cell dedifferentiation. The activation of Rac GTPase was observed in the distal stump of the injured nerves, and a specific Rac inhibitor, a dominant-negative Rac, and Rac1-RNA interference blocked myelin ovoid formation. Together, these findings suggest that dynamic changes in actin in the SLI are essential for initiation of demyelination after peripheral nerve injury.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / chemistry
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Actins / metabolism*
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Aminoquinolines / pharmacology
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Animals
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Axotomy
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Cadherins / metabolism
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Cycloheximide / pharmacology
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Disease Models, Animal
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Early Growth Response Protein 2 / genetics
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Early Growth Response Protein 2 / metabolism
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Electroporation / methods
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / genetics
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Green Fluorescent Proteins / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Myelin P0 Protein / genetics
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Myelin P0 Protein / metabolism
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Myelin Sheath / drug effects
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Myelin Sheath / metabolism*
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Myelin Sheath / ultrastructure
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Neuropeptides / deficiency
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Neuropeptides / genetics
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Organ Culture Techniques
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Polymerization*
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Protein Synthesis Inhibitors / pharmacology
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Pyrimidines / pharmacology
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RNA, Small Interfering / pharmacology
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Sciatic Nerve / pathology*
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Time Factors
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Wallerian Degeneration / pathology*
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Wallerian Degeneration / physiopathology
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rac GTP-Binding Proteins / deficiency
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rac GTP-Binding Proteins / genetics
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rac1 GTP-Binding Protein
Substances
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Actins
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Aminoquinolines
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Cadherins
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Early Growth Response Protein 2
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Myelin P0 Protein
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NSC 23766
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Neuropeptides
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Protein Synthesis Inhibitors
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Pyrimidines
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RNA, Small Interfering
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Rac1 protein, mouse
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Green Fluorescent Proteins
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Cycloheximide
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rac GTP-Binding Proteins
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rac1 GTP-Binding Protein