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.

Actin polymerization is essential for myelin sheath fragmentation during Wallerian degeneration / J. Jung, W. Cai, K. Lee Hyun, M. Pellegatta, K. Shin Yoon, Y. Jang So, J. Suh Duk, L. Wrabetz, M. Feltri, T. Park Hwan. - In: THE JOURNAL OF NEUROSCIENCE. - ISSN 0270-6474. - 31:6(2011 Feb), pp. 2009-2015. [10.1523/JNEUROSCI.4537-10.2011]

Actin polymerization is essential for myelin sheath fragmentation during Wallerian degeneration

M. Feltri
Co-ultimo
;
2011

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.
Settore MED/26 - Neurologia
Settore BIO/17 - Istologia
Settore BIO/13 - Biologia Applicata
feb-2011
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/953376
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