A TIME-SEQUENCE AUTORADIOGRAPHIC STUDY OF THE IN VIVO INCORPORATION OF [1, 2-3H]CHOLESTEROL INTO PERIPHERAL NERVE MYELIN

A time-sequence study of the incorporation and distribution of cholesterol in peripheral nerve myelin was carried out by electron microscope autoradiography. [1,2-3H]Cholesterol was injected into 10-day old mice and the sciatic nerves were dissected out at 10, 20, 40, 60, 90, 120, and 180 min after the injection. 20 min after injection the higher densities of grains due to the presence of [3H]cholesterol were confined to the outer and inner edges of the myelin sheath. Practically no cholesterol was detected in the midzone of the myelin sheath. 1 ½ h after injection, cholesterol showed a wider distribution within the myelin sheath, the higher densities of grains occurring over the two peripheral myelin bands, each approximately 3,100 Å wide. Cholesterol was also present in the center of the myelin sheath but to a considerably lesser extent. 3 h after injection cholesterol appeared homogeneously distributed within the myelin sheath. Schwann cell and axon compartments were also labeled at each time interval studied beginning 20 min postinjection. These observations indicate that preformed cholesterol enters myelin first and almost simultaneously through the inner and outer edges of the sheath; only after 90 min does the density of labeled cholesterol in the central zone of myelin reach the same density as that in the outer and inner zones. These findings suggest that cholesterol used by the nerve fibers in the formation and maintenance of the myelin sheath enters the lamellae from the Schwann cell cytoplasm and from the axon. The possibility of a bidirectional movement of molecules, i.e. from the Schwann cell to the axon and from the axon to the Schwann cell through the myelin sheath, is noted. The results are discussed in the light of recent observations on the exchange, reutilization, and transaxonal movement of cholesterol.

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The Distribution of Electron-Dense Tracers in Peripheral Nerve Fibres

Journal of Cell Science ◽

10.1242/jcs.8.2.541 ◽

1971 ◽

Vol 8 (2) ◽

pp. 541-555

Author(s):

SUSAN M. HALL ◽

P. L. WILLIAMS

Keyword(s):

Schwann Cell ◽

Peripheral Nerve ◽

Myelin Sheath ◽

External Surface ◽

Nerve Fibres ◽

Cell Cytoplasm ◽

Line Region ◽

Periaxonal Space

Two electron-dense tracers, ferritin and lanthanum, have been administered to peripheral nerve fibres, and their uptake has been studied ultrastructurally. It was found that the perineurium was an effective barrier to ferritin in vivo, and the tracer was subsequently injected sub-perineurially. Ferritin uptake over a 120-min period was confined to occasional phagocytic vesicles in perineurial and Schwann cells, and to the nodal gap substance and paranodal periaxonal space. No uptake was observed in the myelin sheath, incisural intraperiod line gap, or in the axoplasm. Soaking fibres in ferritin in vitro resulted in a more generalized cytoplasmic and axoplasmic uptake, although the myelin sheath and Schmidt-Lanterman incisures remained devoid of the tracer. Lanthanum nitrate, included in the fixative solution, delineated the patent incisural intraperiod line gap, and outlined the external surface of the terminal loops of nodal Schwann cell cytoplasm, and the paranodal Schwann cell-axolemmal junction. Unlike ferritin, La3+ penetrated the myelin sheath, being usually confined to the intraperiod line region of the outer lamellae, where it was associated with a widening of the lamellar unit, and an apparent splitting of the intraperiod line. The results are discussed with regard to distribution of extracellular space in peripheral nerve fibres.

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THE ULTRASTRUCTURE OF ADULT VERTEBRATE PERIPHERAL MYELINATED NERVE FIBERS IN RELATION TO MYELINOGENESIS

The Journal of Cell Biology ◽

10.1083/jcb.1.4.271 ◽

1955 ◽

Vol 1 (4) ◽

pp. 271-278 ◽

Cited By ~ 125

Author(s):

J. David Robertson

Keyword(s):

Electron Microscope ◽

Schwann Cell ◽

Cell Surface ◽

Peripheral Nerve ◽

Myelin Sheath ◽

Nerve Fibers ◽

Myelinated Nerve ◽

Thin Sections ◽

Double Membrane ◽

Myelinated Nerve Fibers

Adult chameleon myelinated peripheral nerve fibers have been studied with the electron microscope in thin sections. The outer lamella of the myelin sheath has been found to be connected as a double membrane to the surface of the Schwann cell. The inner lamella is connected as a similar double membrane with the double axon-Schwann membrane. The relations of these double connecting membranes suggest that the layered myelin structure is composed of a double membrane which is closely wound about the axon as a helix. These findings support the new theory of myelinogenesis proposed recently by Geren. The possible significance of these results with respect to cell surface membranes and cytoplasmic double membranes is discussed.

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The in Vivo and Ultrastructural Effects of Injection of Lysophosphatidyl Choline into Myelinated Peripheral Nerve Fibres of the Adult Mouse

Journal of Cell Science ◽

10.1242/jcs.9.3.769 ◽

1971 ◽

Vol 9 (3) ◽

pp. 769-789

Author(s):

SUSAN M. HALL ◽

N. A. GREGSON

Keyword(s):

Schwann Cell ◽

Peripheral Nerve ◽

Myelin Sheath ◽

Time Course ◽

Adult Mouse ◽

Phospholipase A ◽

Nerve Fibres ◽

Lysophosphatidyl Choline

The action of phospholipase A and lysophosphatidyl choline (LPC) on mature, myelinated peripheral nerve fibres has been studied in vivo and electron microscopically, following sub-perineurial injection of these substances. Within 30 min, demyelination was observed in vivo along cylindrico-conical segments, spreading from Schmidt-Lanterman incisures and nodes of Ranvier. By 96 h, all traces of the myelin sheath had disappeared from the area of the lesion, and had been replaced by debris-laden cells lying in chains parallel to one another and the long axis of the fibre. During the next few weeks these cells gradually disappeared, and numerous finely myelinated axons, running between, and in continuity with, the normal fibres proximal and distal to the lesion were observed. If lower concentrations of LPC were used the number of fibres involved decreased, although the demyelinative changes followed the same time-course. Ultrastructurally, demyelination involved progressive disruption and removal of the lamellar sheath, observed initially as a splitting of the intraperiod line within 30 min. Subsequent breakdown resulted in the formation of strands of 4-6 nm repeat material which was further degraded through quintuple- and triple-layered lamellar units to foam-like systems of disorganized lamellar fragments. The Schwann cell and axons appeared to be undamaged by phospholipase A and LPC, and retained their normal impermeability to exogenous ferritin. The significance of the demyelinating capacity of LPC in vivo is discussed in terms of its known action on myelin in vitro, the rapidity and apparent specificity of its action demonstrated in this study, and its potential involvement in pathological demyelination.

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Microneurography: In Vivo Exploration of Impulse Traffic in Human Peripheral Nerve Fibers

Electromyography in CNS Disorders ◽

10.1016/b978-0-409-95144-8.50006-9 ◽

1984 ◽

pp. 19-28 ◽

Cited By ~ 1

Author(s):

Karl-Erik Hagbarth

Keyword(s):

Peripheral Nerve ◽

Nerve Fibers

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Nogo-C Inhibits Peripheral Nerve Regeneration by Regulating Schwann Cell Apoptosis and Dedifferentiation

Frontiers in Neuroscience ◽

10.3389/fnins.2020.616258 ◽

2021 ◽

Vol 14 ◽

Author(s):

Bo Jia ◽

Wei Huang ◽

Yu Wang ◽

Peng Zhang ◽

Zhiwei Wang ◽

...

Keyword(s):

Sciatic Nerve ◽

Schwann Cell ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Schwann Cells ◽

Nerve Injury ◽

Cell Apoptosis ◽

Peripheral Nerve Regeneration ◽

Nerve Fibers ◽

Cell Dedifferentiation

While Nogo protein demonstrably inhibits nerve regeneration in the central nervous system (CNS), its effect on Schwann cells in peripheral nerve repair and regeneration following sciatic nerve injury remains unknown. In this research, We assessed the post-injury expression of Nogo-C in an experimental mouse model of sciatic nerve-crush injury. Nogo-C knockout (Nogo-C–/–) mouse was generated to observe the effect of Nogo-C on sciatic nerve regeneration, Schwann cell apoptosis, and myelin disintegration after nerve injury, and the effects of Nogo-C on apoptosis and dedifferentiation of Schwann cells were observed in vitro. We found that the expression of Nogo-C protein at the distal end of the injured sciatic nerve increased in wild type (WT) mice. Compared with the injured WT mice, the proportion of neuronal apoptosis was significantly diminished and the myelin clearance rate was significantly elevated in injured Nogo-C–/– mice; the number of nerve fibers regenerated and the degree of myelination were significantly elevated in Nogo-C–/– mice on Day 14 after injury. In addition, the recovery of motor function was significantly accelerated in the injured Nogo-C–/– mice. The overexpression of Nogo-C in primary Schwann cells using adenovirus-mediated gene transfer promoted Schwann cells apoptosis. Nogo-C significantly reduced the ratio of c-Jun/krox-20 expression, indicating its inhibition of Schwann cell dedifferentiation. Above all, we hold the view that the expression of Nogo-C increases following peripheral nerve injury to promote Schwann cell apoptosis and inhibit Schwann cell dedifferentiation, thereby inhibiting peripheral nerve regeneration.

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Fibroblasts Colonizing Nerve Conduits Express High Levels of Soluble Neuregulin1, a Factor Promoting Schwann Cell Dedifferentiation

Cells ◽

10.3390/cells9061366 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1366 ◽

Cited By ~ 1

Author(s):

Benedetta E. Fornasari ◽

Marwa El Soury ◽

Giulia Nato ◽

Alessia Fucini ◽

Giacomo Carta ◽

...

Keyword(s):

Schwann Cell ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Schwann Cells ◽

Peripheral Nerve Regeneration ◽

Good Alternative ◽

Cell Dedifferentiation ◽

Nerve Conduits ◽

Early Regeneration

Conduits for the repair of peripheral nerve gaps are a good alternative to autografts as they provide a protected environment and a physical guide for axonal re-growth. Conduits require colonization by cells involved in nerve regeneration (Schwann cells, fibroblasts, endothelial cells, macrophages) while in the autograft many cells are resident and just need to be activated. Since it is known that soluble Neuregulin1 (sNRG1) is released after injury and plays an important role activating Schwann cell dedifferentiation, its expression level was investigated in early regeneration steps (7, 14, 28 days) inside a 10 mm chitosan conduit used to repair median nerve gaps in Wistar rats. In vivo data show that sNRG1, mainly the isoform α, is highly expressed in the conduit, together with a fibroblast marker, while Schwann cell markers, including NRG1 receptors, were not. Primary culture analysis shows that nerve fibroblasts, unlike Schwann cells, express high NRG1α levels, while both express NRG1β. These data suggest that sNRG1 might be mainly expressed by fibroblasts colonizing nerve conduit before Schwann cells. Immunohistochemistry analysis confirmed NRG1 and fibroblast marker co-localization. These results suggest that fibroblasts, releasing sNRG1, might promote Schwann cell dedifferentiation to a “repair” phenotype, contributing to peripheral nerve regeneration.

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Schwann Cell Reactions in Acute and Chronic Segmental Demyelinating Neuropathies

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100100287 ◽

1968 ◽

Vol 26 ◽

pp. 108-109

Author(s):

Roy O. Weller

Keyword(s):

Schwann Cell ◽

Peripheral Nerve ◽

Schwann Cells ◽

Myelin Sheath ◽

Wallerian Degeneration ◽

Demyelinating Disease ◽

Segmental Demyelination ◽

Recovery Stage ◽

Myelin Sheaths ◽

Demyelinating Neuropathies

The length of axon that each Schwann cell myelinates in a normal peripheral nerve is approximately proportional to the diameter of the axon and the thickness of the myelin sheath produced. When segmental demyelination occurs, individual segments, represented by the length of axon covered by one Schwann cell, lose their myelin sheaths but the axons are preserved. This differs from Wallerian degeneration where myelin destruction occurs along the length of a nerve fibre following death of the axon.In experimental diphtheritic neuropathy, an acute segmental demyelinating disease, lysosomes accumulate within the Schwann cells prior to disruption of the myelin sheath; furthermore, the site of initial myelin breakdown appears to be closely related to the collections of lysosomes. The Schwann cell starts to form a new myelin sheath around the axon probably within a few hours of the destruction of the original myelin sheath, and while the latter is being catabolised within lysosomal vacuoles This stage of remyelination follows a similar course to primary myelination, so that the recovery stage is characterised by normal axons with either no myelin, or surrounded by sheaths that are very thin relative to the diameter of the axon.

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Cerebral evoked potentials in human chronic Chagas' disease

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x1989000300003 ◽

1989 ◽

Vol 47 (3) ◽

pp. 274-278 ◽

Cited By ~ 4

Author(s):

O. M. Genovese ◽

Olga P. Sanz ◽

J. Correale ◽

Marcela Garcia Erro ◽

R. E. P. Sica

Keyword(s):

Spinal Cord ◽

Peripheral Nerve ◽

Evoked Potentials ◽

Chagas Disease ◽

Nerve Fibers ◽

Time Interval ◽

Cns Involvement ◽

Cerebral Evoked Potentials ◽

Erb’S Point ◽

Chronic Chagas Disease

Seventy five patients with the diagnosis of chronic Chagas' disease were studied by employing EPs techniques. Two of them had delayed arrival of the signal to the Erb's point and one to the spinal cord when looking at SEPs. TWo patients had increment of the time interval between waves 1st and IIIrd, when studying PEATs. These findings were interpreted as due to peripheral nerve fibers damage, a feature described in previous papers. The, most striking finding was the prolonged time interval between waves N13 and N20 (SEPs) found in two patients and between waves IIIrd and Vth (PEAT) seen in 7 affected subjects. These observations suggested the development of some sort of CNS involvement, perhaps related to myelin damage, in patients who reached the chronic state of the infection.

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