scholarly journals Understanding the mechanisms of entrapment neuropathies

2009 ◽  
Vol 26 (2) ◽  
pp. E7 ◽  
Author(s):  
Khoa Pham ◽  
Ranjan Gupta
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Axonal Injury ◽  
Reciprocal Relationship ◽  
Nerve Compression ◽  
Nerve Tissue ◽  
Myelin Proteins ◽  
Mechanical Stimuli ◽  
Entrapment Neuropathies ◽  
Chronic Nerve Compression

Compression neuropathies are highly prevalent, debilitating conditions with variable functional recovery following surgical decompression. Due to the limited amount of human nerve tissue available for analysis, a number of animal models have been created to help investigators understand the molecular and cellular pathogenesis of chronic nerve compression (CNC) injury. Evidence suggests that CNC injury induces concurrent Schwann cell proliferation and apoptosis in the early stages of the disorder. These proliferating Schwann cells downregulate myelin proteins, leading to local demyelination and remyelination in the region of injury. In addition, the downregulation of myelin proteins, in particular myelin-associated glycoprotein, allows for axonal sprouting. Interestingly, these changes occur in the absence of both morphological and electrophysiological evidence of axonal damage. This is in direct contrast to acute injuries, such as transection or crush, which are characterized by axonal injury followed by Wallerian degeneration. Because the accepted trigger for Schwann cell dedifferentiation is axonal injury, an alternate mechanism for Schwann response must exist in CNC injury. In vitro studies of pure Schwann cells have shown that these cells can respond directly to mechanical stimuli by downregulating myelin proteins and proliferating. These studies suggest that although the reciprocal relationship between neurons and glial cells is maintained, chronic nerve compression injury is a Schwann cell-mediated disease.

Periaxin expression in myelinating Schwann cells: modulation by axon-glial interactions and polarized localization during development

Development ◽  
1995 ◽  
Vol 121 (12) ◽  
pp. 4265-4273 ◽  
Author(s):  
S.S. Scherer ◽  
Y.T. Xu ◽  
P.G. Bannerman ◽  
D.L. Sherman ◽  
P.J. Brophy
Keyword(s):  
Cell Membrane ◽  
Membrane Protein ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Protein Interactions ◽  
Myelin Sheath ◽  
Myelin Proteins ◽  
Developmentally Regulated ◽  
Protein Levels ◽  
Myelin Sheaths

Periaxin is a newly described protein that is expressed exclusively by myelinating Schwann cells. In developing nerves, periaxin is first detected as Schwann cells ensheathe axons, prior to the appearance of the proteins that characterize the myelin sheath. Periaxin is initially concentrated in the adaxonal membrane (apposing the axon) but, during development, as myelin sheaths mature, periaxin becomes predominately localized at the abaxonal Schwann cell membrane (apposing the basal lamina). In permanently axotomized adult nerves, periaxin is lost from the abaxonal and adaxonal membranes, becomes associated with degenerating myelin sheaths and is phagocytosed by macrophages. In crushed nerves, in which axons regenerate and are remyelinated, periaxin is first detected in the adoxonal membrane as Schwann cells ensheathe regenerating axons, but again prior to the appearance of other myelin proteins. Periaxin mRNA and protein levels change in parallel with those of other myelin-related genes after permanent axotomy and crush. These data demonstrate that periaxin is expressed by myelinating Schwann cells in a dynamic, developmentally regulated manner. The shift in localization of periaxin in the Schwann cell after completion of the spiralization phase of myelination suggests that periaxin participates in membrane-protein interactions that are required to stabilize the mature myelin sheath.

Axons regulate Schwann cell expression of the major myelin and NGF receptor genes

Development ◽  
1988 ◽  
Vol 102 (3) ◽  
pp. 499-504 ◽  
Author(s):  
G. Lemke ◽  
M. Chao
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Growth Factor Receptor ◽  
Myelin Proteins ◽  
Ngf Receptor ◽  
Genes Encoding ◽  
Messenger System ◽  
High Level ◽  
Cell Expression ◽  
Inductive Signal

The elaboration of myelin by Schwann cells is triggered by contact with appropriate peripheral axons. Among the most prominent features of this interaction is the activation and high-level expression of the genes encoding the major myelin proteins P0 and Myelin Basic Protein (MBP). Although the initial induction of these genes is thought to be dependent upon contact with axons, neither the inductive signal of the axon nor the receptor and associated second messenger system of the Schwann cell that transduces this signal has been identified. In this report, we demonstrate that expression of the P0 and MBP genes in rapidly myelinating Schwann cells is sharply reduced upon withdrawal of axons, but that this expression can be substantially restored by agents that raise the intracellular concentration of cyclic AMP. We further show that Schwann cell expression of a third gene, i.e. that encoding the Nerve Growth Factor receptor, is strongly activated by the withdrawal of axons, and that this activation is largely independent of cAMP.

Schwann cells upregulate vascular endothelial growth factor secondary to chronic nerve compression injury

2005 ◽  
Vol 31 (4) ◽  
pp. 452-460 ◽  
Author(s):  
Ranjan Gupta ◽  
Michael Gray ◽  
Tom Chao ◽  
David Bear ◽  
Edward Modafferi ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Schwann Cells ◽  
Nerve Compression ◽  
Vascular Endothelial ◽  
Compression Injury ◽  
Chronic Nerve Compression ◽  
Endothelial Growth Factor ◽  
Nerve Compression Injury

scholarly journals Chronic nerve compression alters schwann cell myelin architecture in a murine model

2012 ◽  
Vol 45 (2) ◽  
pp. 231-241 ◽  
Author(s):  
Ranjan Gupta ◽  
Nima Nassiri ◽  
Antony Hazel ◽  
Mary Bathen ◽  
Tahseen Mozaffar
Keyword(s):  
Schwann Cell ◽  
Murine Model ◽  
Nerve Compression ◽  
Chronic Nerve Compression

Human Neurofibromas in Co-Culture with Mouse Neurons

1982 ◽  
Vol 40 ◽  
pp. 194-195
Author(s):  
R.L. Martuza ◽  
T. Liszczak ◽  
A. Okun ◽  
T-Y Wang
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Genetic Disorder ◽  
Cranial Nerves ◽  
Sympathetic Nerves ◽  
Acoustic Neuromas ◽  
Spinal Roots ◽  
Neural Crest Origin ◽  
Multiple Abnormalities ◽  
Other Neoplasms

Neurofibromatosis (NF) is an autosomal dominant genetic disorder with a prevalence of 1/3,000 births. The NF mutation causes multiple abnormalities of various cells of neural crest origin. Schwann cell tumors (neurofibromas, acoustic neuromas) are the most common feature of neurofibromatosis although meningiomas, gliomas, and other neoplasms may be seen. The schwann cell tumors commonly develop from the schwann cells associated with sensory or sympathetic nerves or their ganglia. Schwann cell tumors on ventral spinal roots or motor cranial nerves are much less common. Since the sensory neuron membrane is known to contain a mitogenic factor for schwann cells, we have postulated that neurofibromatosis may be due to an abnormal interaction between the nerve and the schwann cell and that this interaction may be hormonally modulated. To test this possibility a system has been developed in which an enriched schwannoma cell culture can be obtained and co-cultured with pure neurons.

scholarly journals Transposon Mutagenesis-Guided CRISPR/Cas9 Screening Strongly Implicates Dysregulation of Hippo/YAP Signaling in Malignant Peripheral Nerve Sheath Tumor Development

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1584
Author(s):  
Germán L. Vélez-Reyes ◽  
Nicholas Koes ◽  
Ji Hae Ryu ◽  
Gabriel Kaufmann ◽  
Mariah Berner ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Cell Line ◽  
Schwann Cells ◽  
Tumor Suppressor Genes ◽  
Tumor Formation ◽  
Loss Of Function ◽  
Suppressor Genes ◽  
Nerve Sheath

Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive, genomically complex, have soft tissue sarcomas, and are derived from the Schwann cell lineage. Patients with neurofibromatosis type 1 syndrome (NF1), an autosomal dominant tumor predisposition syndrome, are at a high risk for MPNSTs, which usually develop from pre-existing benign Schwann cell tumors called plexiform neurofibromas. NF1 is characterized by loss-of-function mutations in the NF1 gene, which encode neurofibromin, a Ras GTPase activating protein (GAP) and negative regulator of RasGTP-dependent signaling. In addition to bi-allelic loss of NF1, other known tumor suppressor genes include TP53, CDKN2A, SUZ12, and EED, all of which are often inactivated in the process of MPNST growth. A sleeping beauty (SB) transposon-based genetic screen for high-grade Schwann cell tumors in mice, and comparative genomics, implicated Wnt/β-catenin, PI3K-AKT-mTOR, and other pathways in MPNST development and progression. We endeavored to more systematically test genes and pathways implicated by our SB screen in mice, i.e., in a human immortalized Schwann cell-based model and a human MPNST cell line, using CRISPR/Cas9 technology. We individually induced loss-of-function mutations in 103 tumor suppressor genes (TSG) and oncogene candidates. We assessed anchorage-independent growth, transwell migration, and for a subset of genes, tumor formation in vivo. When tested in a loss-of-function fashion, about 60% of all TSG candidates resulted in the transformation of immortalized human Schwann cells, whereas 30% of oncogene candidates resulted in growth arrest in a MPNST cell line. Individual loss-of-function mutations in the TAOK1, GDI2, NF1, and APC genes resulted in transformation of immortalized human Schwann cells and tumor formation in a xenograft model. Moreover, the loss of all four of these genes resulted in activation of Hippo/Yes Activated Protein (YAP) signaling. By combining SB transposon mutagenesis and CRISPR/Cas9 screening, we established a useful pipeline for the validation of MPNST pathways and genes. Our results suggest that the functional genetic landscape of human MPNST is complex and implicate the Hippo/YAP pathway in the transformation of neurofibromas. It is thus imperative to functionally validate individual cancer genes and pathways using human cell-based models, to determinate their role in different stages of MPNST development, growth, and/or metastasis.

scholarly journals Cyclic tensile stimulation enrichment of Schwann cell-laden auxetic hydrogel scaffolds towards peripheral nerve tissue engineering

2020 ◽  
Vol 195 ◽  
pp. 108982 ◽  
Author(s):  
Yi-Wen Chen ◽  
Kan Wang ◽  
Chia-Che Ho ◽  
Chia-Tze Kao ◽  
Hooi Yee Ng ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Nerve Tissue ◽  
Hydrogel Scaffolds ◽  
Nerve Tissue Engineering

scholarly journals Interleukin-4 Regulates the Expression of CD209 and Subsequent Uptake of Mycobacterium leprae by Schwann Cells in Human Leprosy

2010 ◽  
Vol 78 (11) ◽  
pp. 4634-4643 ◽  
Author(s):  
Rosane M. B. Teles ◽  
Stephan R. Krutzik ◽  
Maria T. Ochoa ◽  
Rosane B. Oliveira ◽  
Euzenir N. Sarno ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Primary Cultures ◽  
Mycobacterium Leprae ◽  
Microbial Pathogens ◽  
Interleukin 4 ◽  
Common Mechanism ◽  
Specific Cell

ABSTRACT The ability of microbial pathogens to target specific cell types is a key aspect of the pathogenesis of infectious disease. Mycobacterium leprae, by infecting Schwann cells, contributes to nerve injury in patients with leprosy. Here, we investigated mechanisms of host-pathogen interaction in the peripheral nerve lesions of leprosy. We found that the expression of the C-type lectin, CD209, known to be expressed on tissue macrophages and to mediate the uptake of M. leprae, was present on Schwann cells, colocalizing with the Schwann cell marker, CNPase (2′,3′-cyclic nucleotide 3′-phosphodiesterase), along with the M. leprae antigen PGL-1 in the peripheral nerve biopsy specimens. In vitro, human CD209-positive Schwann cells, both from primary cultures and a long-term line, have a higher binding of M. leprae compared to CD209-negative Schwann cells. Interleukin-4, known to be expressed in skin lesions from multibacillary patients, increased CD209 expression on human Schwann cells and subsequent Schwann cell binding to M. leprae, whereas Th1 cytokines did not induce CD209 expression on these cells. Therefore, the regulated expression of CD209 represents a common mechanism by which Schwann cells and macrophages bind and take up M. leprae, contributing to the pathogenesis of leprosy.

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