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The Journal of Neuroscience, February 2, 2005, 25(5):1179-1187; doi:10.1523/JNEUROSCI.1372-04.2005

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Cellular/Molecular
Degeneration of Myelinated Efferent Fibers Prompts Mitosis in Remak Schwann Cells of Uninjured C-Fiber Afferents

Beth B. Murinson,^1 * David R. Archer,^1 * Yongbo Li,² and John W. Griffin^1,3,4

Departments of ¹Neurology, ²Neurosurgery, ³Neuroscience, and ⁴Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287

The factors inducing normally innervated Schwann cells in peripheral nerve to divide are poorly understood. Transection of the fourth and fifth lumbar ventral roots (L4/5 ventral rhizotomy) of the rat is highly selective, sparing unmyelinated axons and myelinated sensory axons; Wallerian degeneration is restricted to myelinated efferent fibers. We found that L4/5 ventral rhizotomy prompted many normally innervated nonmyelinating (Remak) Schwann cells to enter cell cycle; myelinating Schwann cells of intact (sensory) axons did not. Three days after L4/5 ventral rhizotomy, [³H]thymidine incorporation into Remak Schwann cells increased 30-fold. Schwann cells of degenerating efferents and endoneurial cells also incorporated label. Increased [³H]thymidine incorporation persisted at least 10 d after ventral rhizotomy. Despite Remak Schwann cell proliferation, the morphology of unmyelinated nerve (Remak) bundles was static. Seven days after L5 ventral rhizotomy, Remak Schwann cells in the L5-predominant lateral plantar nerve increased slightly; endoneurial cells doubled. Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-positive nuclei increased dramatically in peripheral nerve after L5 ventral rhizotomy; many of these were macrophage nuclei. In summary, we find that the degeneration of myelinated motor axons produced signals that were mitogenic for nonmyelinating Schwann cells with intact axons but not for myelinating Schwann cells with intact axons.

Key words: apoptosis; C-fiber; degeneration; mitosis; myelin; nerve; Schwann cell; ventral rhizotomy; TUNEL; neuregulin

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Received April 12, 2004; revised November 19, 2004; accepted November 24, 2004.

This article has been cited by other articles:

				L. Decker, C. Desmarquet-Trin-Dinh, E. Taillebourg, J. Ghislain, J.-M. Vallat, and P. Charnay Peripheral myelin maintenance is a dynamic process requiring constant Krox20 expression. J. Neurosci., September 20, 2006; 26(38): 9771 - 9779. [Abstract] [Full Text] [PDF]

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