Myelin sheath survival following axonal degeneration in doubly myelinated nerve fibers

Abstract

Axonal contact plays a critical role in initiating myelin formation by Schwann cells. However, recent studies of “double myelination” have indicated that myelin maintenance continues in Schwann cells completely displaced from physical contact with the axon. This raises the possibility either that diffusible trophic factors are produced by the axon, or that the axon is not required for myelin maintenance by these displaced Schwann cells. To test these hypotheses, the axons involved in double myelination in the mouse superior cervical ganglion (SCG) were transected surgically by a transganglionic lesion. The inferior pole of the SCG was resected to limit axonal regeneration. This method produced a typical Wallerian pattern of degeneration in the superior pole, without compromising the blood supply or introducing nonspecific trauma. EM analysis at 1 and 5 d postoperatively showed that initially the axon degenerated, followed by breakdown of the inner myelin sheath. In those configurations where the outer Schwann cell was only partly displaced from the axon, the outer myelin sheath degenerated simultaneously. However, in completely displaced internodes the outer sheath survived degeneration of the axon and inner sheath. Outer internodes remained intact for at least 5 weeks after transection (the longest time point in this study), at which time they enclosed reorganized processes of the inner Schwann cells, their basal lamina, and numerous collagen fibrils. Axonal regeneration within surviving outer internodes was rare and was characterized by the development of typical Remak ensheathment by the inner Schwann cells. We conclude that in the mouse SCG, myelin maintenance does not depend on the continued presence of the axon. These data suggest further that myelin breakdown in Wallerian degeneration may be initiated by mechanisms other than absence of a viable axon.

Elevated Phosphatidylinositol 3,4,5-Trisphosphate in Glia Triggers Cell-Autonomous Membrane Wrapping and Myelination

“…6A-C) strongly suggest an active wrapping process rather than secondary collagen ingrowth. Axon-independent myelination, as reported here, is also different from "double myelination" that can occasionally result from the displacement of one internode by the interposition of another myelinating Schwann cell (Kidd and Heath, 1991).…”

Microanatomy of Axon/Glial Signaling during Wallerian Degeneration

“…During Wallerian degeneration, Schwann cell responses are initiated by a positive signaling event that requires close contact with damaged axons (Kidd and Heath, 1991). Exposure to recombinant neuregulin in vitro can induce demyelination that mimics the early response of Schwann cells to nerve damage in animals .…”

“…Because Wallerian degeneration is initiated only within Schwann cells that contact the axon (Kidd and Heath, 1991), we used immunostaining techniques and deconvolving microscopy to determine the subcellular localization of erbB2 in myelinated axons. In teased nerve fiber preparations of rat sciatic nerve, we occasionally noted weak erbB2 immunostaining at the perinu- Early and late activation of erbB2 after axotomy.…”

“…The behavior of doubly myelinating Schwann cells indicates that close contact with the axon is required for delivery of this signal (Kidd and Heath, 1991). Double myelination results from displacement of a myelinating Schwann cell from axonal contact because of invasion of another Schwann cell at a node.…”

A Quantitative Ultrastructural Study of the Optic Nerve of the Chameleon

“…In the mammalian optic nerve, similar anomalies have been ascribed to degenerative processes [Cooke, 1974;Sturrock, 1987;Kidd and Heath, 1991], or to developmental accidents [Peters et al, 1976]; it is somewhat curious that these anomalies have not been described in the chelonian optic nerve [Geri et al, 1982;Woodbury and Ulinski, 1986]. Their presence in metamorphosing amphibians suggests that these anomalies might be related to some unidentified dynamic aspect of neuronal organization, and further studies are indicated to elucidate the question.…”