scholarly journals Distribution and role in regeneration of N-CAM in the basal laminae of muscle and Schwann cells.

1988 ◽  
Vol 107 (2) ◽  
pp. 707-719 ◽  
Author(s):  
F Rieger ◽  
M Nicolet ◽  
M Pinçon-Raymond ◽  
M Murawsky ◽  
G Levi ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Basal Lamina ◽  
Close Association ◽  
Axon Terminals ◽  
Muscle Extract ◽  
Cell Processes ◽  
Myelinating Schwann Cell

The neural cell adhesion molecule (N-CAM) is a membrane glycoprotein involved in neuron-neuron and neuron-muscle adhesion. It can be synthesized in various forms by both nerve and muscle and it becomes concentrated at the motor endplate. Biochemical analysis of a frog muscle extract enriched in basal lamina revealed the presence of a polydisperse, polysialylated form of N-CAM with an average Mr of approximately 160,000 as determined by SDS-PAGE, which was converted to a form of 125,000 Mr by treatment with neuraminidase. To define further the role of N-CAM in neuromuscular junction organization, we studied the distribution of N-CAM in an in vivo preparation of frog basal lamina sheaths obtained by inducing the degeneration of both nerve and muscle fibers. Immunoreactive material could be readily detected by anti-N-CAM antibodies in such basal lamina sheaths. Ultrastructural analysis using immunogold techniques revealed N-CAM in close association with the basal lamina sheaths, present in dense accumulation at places that presumably correspond to synaptic regions. N-CAM epitopes were also associated with collagen fibrils in the extracellular matrix. The ability of anti-N-CAM antibodies to perturb nerve regeneration and reinnervation of the remaining basal lamina sheaths was then examined. In control animals, myelinating Schwann cells wrapped around the regenerated axon and reinnervation occurred only at the old synaptic areas; new contacts between nerve and basal lamina had a terminal Schwann cell capping the nerve terminal. In the presence of anti-N-CAM antibodies, three major abnormalities were observed in the regeneration and reinnervation processes: (a) regenerated axons in nerve trunks that had grown back into the old Schwann cell basal lamina were rarely associated with myelinating Schwann cell processes, (b) ectopic synapses were often present, and (c) many of the axon terminals lacked a terminal Schwann cell capping the nerve-basal lamina contact area. These results suggest that N-CAM may play an important role not only in the determination of synaptic areas but also in Schwann cell-axon interactions during nerve regeneration.

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

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1366 ◽  
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.

scholarly journals Normal basal laminas are realized on dystrophic Schwann cells in dystrophic in equilibrium shiverer chimera nerves.

1984 ◽  
Vol 99 (5) ◽  
pp. 1831-1837 ◽  
Author(s):  
A C Peterson ◽  
G M Bray
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Cell Population ◽  
Basal Lamina ◽  
Mutant Phenotype ◽  
Normal Product ◽  
Pathogenetic Mechanisms ◽  
Dystrophic Mice

Multiple discontinuities are observed in the basal laminas of Schwann cells in mature dystrophic mice. To explore the pathogenesis of this abnormality we have exploited a dystrophic in equilibrium shiverer mouse chimera preparation in which both the basal lamina phenotype and the genotype of myelin-forming Schwann cells can be determined. If the basal lamina abnormality were to arise from an intrinsic deficiency of the dystrophic Schwann cell itself, only those Schwann cells of dystrophic genotype could express the mutant phenotype, whereas the coexisting population of shiverer Schwann cells should express typically normal basal laminas. No such distinction was observed; rather both dystrophic and shiverer Schwann cells were found to express relatively normal basal laminas and two pathogenetic mechanisms remain theoretical possibilities. The dystrophic Schwann cell population may be intrinsically defective but also may be rescued by obtaining the normal product of the dy locus synthesized by the coexisting shiverer cells. Alternatively, an extra Schwann cell deficiency existing within dystrophic mice may be normalized by shiverer cells and the normal intrinsic potential of both dystrophic and shiverer Schwann cells can then be realized. Regardless of the exact mechanism underlying these findings, some extracellularly mediated influence, emanating in vivo from shiverer cells, is capable of ameliorating the basal lamina deficiency typically expressed by dystrophic Schwann cells.

scholarly journals Matrix metalloproteinase 7 promoted Schwann cell migration and myelination after rat sciatic nerve injury

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Hongkui Wang ◽  
Ping Zhang ◽  
Jun Yu ◽  
Fuchao Zhang ◽  
Wenzhao Dai ◽  
...  
Keyword(s):  
Cell Migration ◽  
Sciatic Nerve ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Peripheral Nerve Regeneration ◽  
Schwann Cell Migration

AbstractSchwann cells experience de-differentiation, proliferation, migration, re-differentiation and myelination, and participate in the repair and regeneration of injured peripheral nerves. Our previous sequencing analysis suggested that the gene expression level of matrix metalloproteinase 7 (MMP7), a Schwann cell-secreted proteolytic enzyme, was robustly elevated in rat sciatic nerve segments after nerve injury. However, the biological roles of MMP7 are poorly understood. Here, we exposed primary cultured Schwann cells with MMP7 recombinant protein and transfected siRNA against MMP7 into Schwann cells to examine the effect of exogenous and endogenous MMP7. Meanwhile, the effects of MMP7 in nerve regeneration after sciatic nerve crush in vivo were observed. Furthermore, RNA sequencing and bioinformatic analysis of Schwann cells were conducted to show the molecular mechanism behind the phenomenon. In vitro studies showed that MMP7 significantly elevated the migration rate of Schwann cells but did not affect the proliferation rate of Schwann cells. In vivo studies demonstrated that increased level of MMP7 contributed to Schwann cell migration and myelin sheaths formation after peripheral nerve injury. MMP7-mediated genetic changes were revealed by sequencing and bioinformatic analysis. Taken together, our current study demonstrated the promoting effect of MMP7 on Schwann cell migration and peripheral nerve regeneration, benefited the understanding of cellular and molecular mechanisms underlying peripheral nerve injury, and thus might facilitate the treatment of peripheral nerve regeneration in clinic.

scholarly journals Axonal regulation of Schwann cell integrin expression suggests a role for alpha 6 beta 4 in myelination.

1993 ◽  
Vol 123 (5) ◽  
pp. 1223-1236 ◽  
Author(s):  
S Einheber ◽  
T A Milner ◽  
F Giancotti ◽  
J L Salzer
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Basal Lamina ◽  
Cell Contact ◽  
Myelin Associated Glycoprotein ◽  
Dorsal Root Ganglia Neurons ◽  
Outer Plasma Membrane

Ensheathment and myelination of axons by Schwann cells in the peripheral nervous system requires contact with a basal lamina. The molecular mechanism(s) by which the basal lamina promotes myelination is not known but is likely to reflect the activity of integrins expressed by Schwann cells. To initiate studies on the role of integrins during myelination, we characterized the expression of two integrin subunits, beta 1 and beta 4, in an in vitro myelination system and compared their expression to that of the glial adhesion molecule, the myelin-associated glycoprotein (MAG). In the absence of neurons, Schwann cells express significant levels of beta 1 but virtually no beta 4 or MAG. When Schwann cells are cocultured with dorsal root ganglia neurons under conditions promoting myelination, expression of beta 4 and MAG increased dramatically in myelinating cells, whereas beta 1 levels remained essentially unchanged. (In general agreement with these findings, during peripheral nerve development in vivo, beta 4 levels also increase during the period of myelination in sharp contrast to beta 1 levels which show a striking decrease.) In cocultures of neurons and Schwann cells, beta 4 and MAG appear to colocalize in nascent myelin sheaths but have distinct distributions in mature sheaths, with beta 4 concentrated in the outer plasma membrane of the Schwann cell and MAG localized to the inner (periaxonal) membrane. Surprisingly, beta 4 is also present at high levels with MAG in Schmidt-Lanterman incisures. Immunoprecipitation studies demonstrated that primary Schwann cells express beta 1 in association with the alpha 1 and alpha 6 subunits, while myelinating Schwann cells express alpha 6 beta 4 and possibly alpha 1 beta 1. beta 4 is also downregulated during Wallerian degeneration in vitro, indicating that its expression requires continuous Schwann cell contact with the axon. These results indicate that axonal contact induces the expression of beta 4 during Schwann cell myelination and suggest that alpha 6 beta 4 is an important mediator of the interactions of myelinating Schwann cells with the basal lamina.

Resorbable Structures for Schwann Cell Enhanced Peripheral Nerve Regeneration

1998 ◽  
Vol 550 ◽  
Author(s):  
A.E. Silva ◽  
LC. Summerhayes ◽  
D.J. Trantolo ◽  
D.L. Wise ◽  
M.V. Catftaneo ◽  
...  
Keyword(s):  
Growth Factor ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Peripheral Nerve Regeneration ◽  
Cell Movement ◽  
Regenerative Process

AbstractSchwann cells play a dual role serving as a physical framework for regenerating nerves, providing extracellular matrix proteins and specific adhesion molecules facilitating attachment and cell movement, and as a source of stimulatory factors mediated by the release or reception of different ligands important in growth and cell signaling events. To investigate the role of one such ligand, glial growth factor (GGF), in peripheral nerve regeneration, a bioabsorbable nerve guide, prepared from a poly(lactic-co-glycolic) acid (PLGA) foam was seeded with autogenous Schwann cells in the presence and absence of growth factor and evaluated in vivo using a rat sciatic nerve regeneration model. Four weeks post-operatively peripheral nerve regeneration was evident. The resorbable foam implant demonstrated extensive neo-vascularization in and around the guide with no evidence of an inflammatory response or encapsulation. The study showed a statistically significant increase in all measured parameters of nerve regeneration in the presence of GGF. Increased numbers of blood vessels in the regenerated tissue accompanied increased total axon counts after twelve weeks. The addition of exogenous Schwann cells resulted in reduced total axon counts perhaps due to the competition for limited growth factors released by the regenerating tissues. The Schwann cell groups, however, displayed the highest myelination indices recorded likely reflecting the role of Schwann cells in the myelination process. Measurements of conduction velocities (EMGs) revealed the highest conductance velocities recorded in nerves regenerated in the presence of both GGF and Schwann cells. Clearly, the inclusion of GGF in the nerve regenerative process is beneficial with respect to both the generation of new axons and the establishment of a functional endpoint.

Characterisation of cis-acting sequences reveals a biphasic, axon-dependent regulation of Krox20 during Schwann cell development

Development ◽  
2002 ◽  
Vol 129 (1) ◽  
pp. 155-166 ◽  
Author(s):  
Julien Ghislain ◽  
Carole Desmarquet-Trin-Dinh ◽  
Martine Jaegle ◽  
Dies Meijer ◽  
Patrick Charnay ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Schwann Cell ◽  
Dependent Manner ◽  
Cis Acting ◽  
Pou Domain ◽  
Cell Element ◽  
Schwann Cell Development ◽  
Myelinating Schwann Cell ◽  
Sciatic Nerve Regeneration

In Schwann cells (SC), myelination is controlled by the transcription factor gene Krox20/Egr2. Analysis of cis-acting elements governing Krox20 expression in SC revealed the existence of two separate elements. The first, designated immature Schwann cell element (ISE), was active in immature but not myelinating SC, whereas the second, designated myelinating Schwann cell element (MSE), was active from the onset of myelination to adulthood in myelinating SC. In vivo sciatic nerve regeneration experiments demonstrated that both elements were activated during this process, in an axon-dependent manner. Together the activity of these elements reproduced the profile of Krox20 expression during development and regeneration. Genetic studies showed that both elements were active in a Krox20 mutant background, while the activity of the MSE, but likely not of the ISE, required the POU domain transcription factor Oct6 at the time of myelination. The MSE was localised to a 1.3 kb fragment, 35 kb downstream of Krox20. The identification of multiple Oct6 binding sites within this fragment suggested that Oct6 directly controls Krox20 transcription. Taken together, these data indicate that, although Krox20 is expressed continuously from 15.5 dpc in SC, the regulation of its expression is a biphasic, axon-dependent phenomenon involving two cis-acting elements that act in succession during development. In addition, they provide insight into the complexity of the transcription factor regulatory network controlling myelination.

Schwann cell basal lamina and central nerve regeneration

1985 ◽  
Vol 1 ◽  
pp. S131
Author(s):  
Chizuka Ide ◽  
Satoru Onodera ◽  
Koujiro Tohyama ◽  
Reiko Yokota ◽  
Tohru Nitatori
Keyword(s):  
Schwann Cell ◽  
Nerve Regeneration ◽  
Basal Lamina

Axonal signalling and the making of olfactory ensheathing cells: a hypothesis

2006 ◽  
Vol 2 (3) ◽  
pp. 217-224 ◽  
Author(s):  
KONSTANTIN WEWETZER ◽  
GUDRUN BRANDES
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Specific Interaction ◽  
Neurotrophin Receptor ◽  
Olfactory Ensheathing Cells ◽  
Experimental Conditions ◽  
Neural Repair ◽  
Ensheathing Cells

Olfactory ensheathing cells (OECs) are Schwann cell-like glial cells of the olfactory system that promote neural repair under experimental conditions. It is a matter of debate in how far OECs resemble Schwann cells and whether they possess specific properties. Although OECs have been characterized mainly with respect to their regenerative effects after transplantation, both their cellular identity and the regulating factors involved have remained vague. The aim of this article is to define OEC and Schwann-cell identity in molecular terms, and to discuss crucial factors that are involved in determination in vitro and in vivo. Distinct OEC features such as the down-regulation of the low affinity neurotrophin receptor p75NTR by neuronal contact are apparent in vivo under physiological conditions, whereas OECs acquire a Schwann cell-like phenotype and up-regulate p75NTR expression in vitro and following transplantation into the lesioned spinal cord. This might indicate that establishment of the OEC phenotype depends on specific axonal stimuli. In this review we hypothesize that OECs and Schwann cells possess malleable cellular phenotypes that acquire distinct features only upon specific interaction with their natural neuronal partner. This concept is consistent with previous findings in vitro and in vivo, and might be relevant for studies that use OECs and Schwann cells for nervous system repair.

PERIPHERAL NERVE REGENERATION THROUGH NERVE GUIDES FILLED WITH BILOBALIDE AND SCHWANN CELLS

2006 ◽  
Vol 18 (01) ◽  
pp. 8-12
Author(s):  
MING-CHIN LU ◽  
YUNG-HISEN CHANG ◽  
LEIH-CHIH CHIANG ◽  
HAI-TING WANG ◽  
CHUN-YUAN CHENG ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Chinese Medicine ◽  
Sciatic Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Peripheral Nerve Regeneration ◽  
New Approach ◽  
Nerve Guides ◽  
Growth Promoting

The present study provides in vivo trials of silicone rubber chambers filled with different concentrations of bilobalide (0, 50, 100, 200, 400 μM) and Schwann cells (1.5 × 105 cell/ml) in a 1:1 volumetric addition to bridge a 15 mm sciatic nerve defect in rats. At the conclusion of 8 weeks, histological technique was used to evaluate the functional recovery of the nerve. In the groups receiving the Schwann cells and bilobalide at 50, 100, 200 and 400 μM, 44% (4 of 9, one died during experiment), 50% (5 of 10), 30% (3 of 10), and 60% (6 of 10) of the animals exhibiting a regenerated nerve cable across the 15-mm gap, respectively. In comparison, 50% (5 of 10) of the animals in the group with Schwann cells only showed such regenerated nerve cables. Although the adding of bilobalide did not promote the nerve growth-promoting capability of Schwann cells in the nerve guides, the techniques we used in this study provided a new approach combining Chinese medicine and tissue engineering to nerve regeneration.

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