Effects of an Inhibitor of Proteoglycan Biosynthesis on Neuron-Induced Schwann Cell Proliferation and Basal Lamina Formation By Schwann Cells

1987 ◽  
pp. 127-139 ◽  
Author(s):  
N. Ratner ◽  
C. Eldridge ◽  
R. Bunge ◽  
L. Glaser
Keyword(s):  
Cell Proliferation ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Basal Lamina

scholarly journals Cerebellar granule cells contain a membrane mitogen for cultured Schwann cells.

1989 ◽  
Vol 108 (2) ◽  
pp. 607-611 ◽  
Author(s):  
P W Mason ◽  
J W Bigbee ◽  
G H DeVries
Keyword(s):  
Cell Proliferation ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Cell Cultures ◽  
Granule Cell ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Proteoglycan Synthesis ◽  
Cerebellar Granule ◽  
Mitogenic Signal

Proliferation of Schwann cells is one of the first events that occurs after contact with a growing axon. To further define the distribution and properties of this axonal mitogen, we have (a) cocultured cerebellar granule cells, which lack glial ensheathment in vivo with Schwann cells; and (b) exposed Schwann cell cultures to isolated granule cell membranes. Schwann cells cocultured with granule cells had a 30-fold increase in the labeling index over Schwann cells cultured alone, suggesting that the mitogen is located on the granule cell surface. Inhibition of granule cell proteoglycan synthesis caused a decrease in the granule cells' ability to stimulate Schwann cell proliferation. Membranes isolated from cerebellar granule cells when added to Schwann cell cultures caused a 45-fold stimulation in [3H]thymidine incorporation. The granule cell mitogenic signal was heat and trypsin sensitive and did not require lysosomal processing by Schwann cells to elicit its proliferative effect. The ability of granule cells and their isolated membranes to stimulate Schwann cell proliferation suggests that the mitogenic signal for Schwann cells is a ubiquitous factor present on all axons regardless of their ultimate state of glial ensheathment.

scholarly journals Calcitonin gene-related peptide promotes Schwann cell proliferation.

1995 ◽  
Vol 129 (3) ◽  
pp. 789-796 ◽  
Author(s):  
L Cheng ◽  
M Khan ◽  
A W Mudge
Keyword(s):  
Cell Proliferation ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Neutral Endopeptidase ◽  
Calcitonin Gene Related Peptide ◽  
Intracellular Camp ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Glial Growth Factor

Schwann cells in culture divide in response to defined mitogens such as PDGF and glial growth factor (GGF), but proliferation is greatly enhanced if agents such as forskolin, which increases Schwann cell intracellular cAMP, are added at the same time as PDGF or GGF (Davis, J. B., and P. Stroobant. 1990. J. Cell Biol. 110:1353-1360). The effect of forskolin is probably due to an increase in numbers of PDGF receptors (Weinmaster, G., and G. Lemke. 1990. EMBO (Eur. Mol. Biol. Organ.) J. 9:915-920. Neuropeptides and beta-adrenergic agonists have been reported to have no effect on potentiating the mitogenic response of either PDGF or GGF. We show that the neuropeptide calcitonin gene-related peptide (CGRP) increases Schwann cell cAMP levels, but the cells rapidly desensitize. We therefore stimulated the cells in pulsatile fashion to partly overcome the effects of desensitization and show that CGRP can synergize with PDGF to stimulate Schwann cell proliferation, and that CGRP is as effective as forskolin in the pulsatile regime. CGRP is a good substrate for the neutral endopeptidase 24.11. Schwann cells in vivo have this protease on their surface, so the action of CGRP could be terminated by this enzyme and desensitization prevented. We therefore suggest that CGRP may play an important role in stimulating Schwann cell proliferation by regulating the response of mitogenic factors such as PDGF.

scholarly journals Jab1 regulates Schwann cell proliferation and axonal sorting through p27

2013 ◽  
Vol 211 (1) ◽  
pp. 29-43 ◽  
Author(s):  
Emanuela Porrello ◽  
Cristina Rivellini ◽  
Giorgia Dina ◽  
Daniela Triolo ◽  
Ubaldo Del Carro ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Cell Cycle Progression ◽  
Cell Number ◽  
Cycle Progression ◽  
Neuregulin 1 ◽  
Regulatory Molecule ◽  
Axonal Sorting

Axonal sorting is a crucial event in nerve formation and requires proper Schwann cell proliferation, differentiation, and contact with axons. Any defect in axonal sorting results in dysmyelinating peripheral neuropathies. Evidence from mouse models shows that axonal sorting is regulated by laminin211– and, possibly, neuregulin 1 (Nrg1)–derived signals. However, how these signals are integrated in Schwann cells is largely unknown. We now report that the nuclear Jun activation domain–binding protein 1 (Jab1) may transduce laminin211 signals to regulate Schwann cell number and differentiation during axonal sorting. Mice with inactivation of Jab1 in Schwann cells develop a dysmyelinating neuropathy with axonal sorting defects. Loss of Jab1 increases p27 levels in Schwann cells, which causes defective cell cycle progression and aberrant differentiation. Genetic down-regulation of p27 levels in Jab1-null mice restores Schwann cell number, differentiation, and axonal sorting and rescues the dysmyelinating neuropathy. Thus, Jab1 constitutes a regulatory molecule that integrates laminin211 signals in Schwann cells to govern cell cycle, cell number, and differentiation. Finally, Jab1 may constitute a key molecule in the pathogenesis of dysmyelinating neuropathies.

scholarly journals Neuron Regeneration and Proliferation Effects of Danshen and Tanshinone IIA

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Jui-Lung Shen ◽  
Yueh-Sheng Chen ◽  
Jing-Ying Lin ◽  
Yun-Chen Tien ◽  
Wen-Huang Peng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Map Kinases ◽  
Mapk Signaling ◽  
Tanshinone Iia ◽  
Dependent Manner ◽  
Neuron Regeneration

This study evaluates the proliferative effects of danshen and its monomer extract, tanshinone IIA, on Schwann cell proliferation. A piece of silicone rubber was guided across a 15-mm gap in the sciatic nerve of a rat. This nerve gap was then filled with different concentrations of danshen (0–100 mg/mL). The results showed that danshen increased the expressions of uPA, cyclin D1, E and ERK, JNK, and P38 MAP kinases via the FGF-2 signaling pathway in a dose-dependent manner. RSC96, Schwann cells were also administered with danshen (0, 20, 40, 60, 80, and 100 μg/mL) and tanshinone IIA (0, 2, 4, 6, 8, and 10 μg/mL). In lower concentrations, danshen and tanshinone IIA exhibited an apparent effect on Schwann cells. Similar effects were also demonstrated in the FGF-2-uPA regulating cascade and cell cycle proliferative protein results. Schwann cell migration was elevated as well. We used MAPK-signaling chemical inhibitors and identified the proliferative effects of danshen and tanshinone IIA as MAPK-signaling dependent. The results from thein vitrosystems indicate that danshen and tanshinone IIA can be used to induce Schwann cell proliferation, andin vivoresults potentially suggest that danshen and tanshinone IIA might enhance neuron regeneration.

Acetylcholine inhibits cell cycle progression in rat Schwann cells by activation of the M2 receptor subtype

2007 ◽  
Vol 3 (4) ◽  
pp. 269-279 ◽  
Author(s):  
Simona Loreti ◽  
Ruggero Ricordy ◽  
M. Egle De Stefano ◽  
Gabriella Augusti-Tocco ◽  
Ada Maria Tata
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Cell Cycle Progression ◽  
Receptor Activation ◽  
Neonatal Rat ◽  
Receptor Subtype ◽  
Cell Nuclei

AbstractCultures of Schwann cells from neonatal rat sciatic nerves were treated with acetylcholine agonists and the effects on cell proliferation evaluated. 3[H]-thymidine incorporation shows that acetylcholine (ACh) receptor agonists inhibit cell proliferation, and FACS analysis demonstrates cell-cycle arrest and accumulation of cells in the G1 phase. The use of arecaidine, a selective agonist of muscarinic M2 receptors reveals that this effect depends mainly on M2 receptor activation. The arecaidine dependent-block in G1 is reversible because removal of arecaidine from the culture medium induces progression to the S phase. The block of the G1-S transition is also characterized by modulation of the expression of several cell-cycle markers. Moreover, treatment with ACh receptor agonist causes both a decrease in the PCNA protein levels in Schwann cell nuclei and an increase in p27 and p53 proteins. Finally, immuno-electron microscopy demonstrates that M2 receptors are expressed by Schwann cells in vivo. These results indicate that ACh, by modulating Schwann cell proliferation through M2 receptor activation, might contribute to their progression to a more differentiated phenotype.

scholarly journals Coordinate control of axon defasciculation and myelination by laminin-2 and -8

2005 ◽  
Vol 168 (4) ◽  
pp. 655-666 ◽  
Author(s):  
Dongren Yang ◽  
Jesse Bierman ◽  
Yukie S. Tarumi ◽  
Yong-Ping Zhong ◽  
Reshma Rangwala ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Dominant Role ◽  
Pathogenic Mechanism ◽  
Structural Defects ◽  
Autocrine Factors ◽  
Coordinate Control

Schwann cells form basal laminae (BLs) containing laminin-2 (Ln-2; heterotrimer α2β1γ1) and Ln-8 (α4β1γ1). Loss of Ln-2 in humans and mice carrying α2-chain mutations prevents developing Schwann cells from fully defasciculating axons, resulting in partial amyelination. The principal pathogenic mechanism is thought to derive from structural defects in Schwann cell BLs, which Ln-2 scaffolds. However, we found loss of Ln-8 caused partial amyelination in mice without affecting BL structure or Ln-2 levels. Combined Ln-2/Ln-8 deficiency caused nearly complete amyelination, revealing Ln-2 and -8 together have a dominant role in defasciculation, and that Ln-8 promotes myelination without BLs. Transgenic Ln-10 (α5β1γ1) expression also promoted myelination without BL formation. Rather than BL structure, we found Ln-2 and -8 were specifically required for the increased perinatal Schwann cell proliferation that attends myelination. Purified Ln-2 and -8 directly enhanced in vitro Schwann cell proliferation in collaboration with autocrine factors, suggesting Lns control the onset of myelination by modulating responses to mitogens in vivo.

scholarly journals FAK is required for axonal sorting by Schwann cells

2007 ◽  
Vol 176 (3) ◽  
pp. 277-282 ◽  
Author(s):  
Matthew Grove ◽  
Noboru H. Komiyama ◽  
Klaus-Armin Nave ◽  
Seth G. Grant ◽  
Diane L. Sherman ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Cell Number ◽  
Erbb Receptor ◽  
Erbb2 Receptor ◽  
Transduction Mechanisms ◽  
Axonal Sorting ◽  
Developing Nervous System ◽  
Stimulate Cell Proliferation

Signaling by laminins and axonal neuregulin has been implicated in regulating axon sorting by myelin-forming Schwann cells. However, the signal transduction mechanisms are unknown. Focal adhesion kinase (FAK) has been linked to α6β1 integrin and ErbB receptor signaling, and we show that myelination by Schwann cells lacking FAK is severely impaired. Mutant Schwann cells could interdigitate between axon bundles, indicating that FAK signaling was not required for process extension. However, Schwann cell FAK was required to stimulate cell proliferation, suggesting that amyelination was caused by insufficient Schwann cells. ErbB2 receptor and AKT were robustly phosphorylated in mutant Schwann cells, indicating that neuregulin signaling from axons was unimpaired. These findings demonstrate the vital relationship between axon defasciculation and Schwann cell number and show the importance of FAK in regulating cell proliferation in the developing nervous system.

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 Studies of Schwann cell proliferation. I. An analysis in tissue culture of proliferation during development, Wallerian degeneration, and direct injury.

1980 ◽  
Vol 84 (3) ◽  
pp. 739-752 ◽  
Author(s):  
J L Salzer ◽  
R P Bunge
Keyword(s):  
Cell Proliferation ◽  
Tissue Culture ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Wallerian Degeneration ◽  
Variable Response ◽  
Experimental Conditions ◽  
Fetal Rat ◽  
Direct Injury ◽  
Dividing Cells

In this paper the stimuli for and pattern of Schwann cell proliferation are defined under various experimental conditions. We used a tissue culture system in which fetal rat dorsal root ganglia, treated to eliminate contaminating fibroblasts (Wood, P., 1976, Brain Res. 115:361--375), appear to recapitulate many aspects of the developing peripheral nervous system. We observed that: (a) proliferation of Schwann cells on neurites is initially rapid, but, as each neurite becomes fully ensheathed, division slows considerably and is confined to the periphery of the outgrowth; (b) during the period of rapid proliferation, excision of the ganglion causes a rapid decay in the number of dividing cells; (c) excision of the ganglion from more established cultures in which there was little ongoing proliferation resulted in a small increase in labeling at the site of excision for all Schwann cells and a substantial increase in labeling for myelin-related cells with a peak labeling period at 4 d; (d) direct mechanical injury during Wallerian degeneration is mitogenic for Schwann cells; (e) a variety of potential mitogens failed to stimulate Schwann cell proliferation, and (f) replated cells have a slightly higher level of proliferation and show a small and variable response to the addition of cAMP.

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