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Schwann cells are the myelinating glia cells of the peripheral nervous system (PNS) and can become targets of an autoimmune response in inflammatory neuropathies like the Guillain‐Barré syndrome (GBS). Professional antigen presenting cells (APCs) are known to promote autoimmune responses in target tissues by presenting self‐antigens. Other cell types could participate in local autoimmune responses...
Production of nerve growth factor (NGF) from Schwann cells (SCs) progressively declines in the distal stump, if axonal regeneration is staggered across the suture site after peripheral nerve injuries. This may be an important factor limiting the outcome of nerve injury repair. Thus far, extensive efforts are devoted to modulating NGF production in cultured SCs, but little has been achieved. In the...
Reorganization of the actin cytoskeleton is necessary for Schwann cell proliferation, migration and for the morphological changes associated with sorting, ensheathing and myelination of axons. Such reorganization requires regulated severing and depolymerization of actin filaments. Gelsolin is an actin filament severing protein expressed in many cell types including Schwann cells. Using Gelsolin knockout...
Glucocorticoids improve the symptoms of peripheral nerve disorders, such as carpal tunnel syndrome and peripheral neuropathy. The effects of glucocorticoids are mainly anti‐inflammatory, but the mechanisms of their effects in peripheral nerve disorders remain unclear. Schwann cells of the peripheral nerves express glucocorticoid receptors (GR), and glucocorticoids enhance the rate of myelin formation...
Understanding the mechanisms that control myelin formation is essential for the development of demyelinating diseases treatments. All‐trans‐retinoic acid (RA) plays an essential role during the development of the nervous system as a potent regulator of morphogenesis, cell growth, and differentiation. In this study, we show that RA is also a potent inhibitor of peripheral nervous system (PNS) myelination...
Toll‐like receptors comprise a family of evolutionary conserved pattern recognition receptors that act as a first defense line in the innate immune system. Upon stimulation with microbial ligands, they orchestrate the induction of a host defense response by activating different signaling cascades. Interestingly, they appear to detect the presence of endogenous signals of danger as well and as such,...
Peripheral nerve function depends on a regulated process of axon and Schwann cell development. Schwann cells interact with peripheral neurons to sort and ensheath individual axons. Ablation of laminin γ1 in the peripheral nervous system (PNS) arrests Schwann cell development prior to radial sorting of axons. Peripheral nerves of laminin‐deficient animals are disorganized and hypomyelinated. In this...
Wallerian degeneration (WD) is an inflammatory process of nerve degeneration, which occurs more rapidly in the peripheral nervous system compared with the central nervous system, resulting, respectively in successful and aborted axon regeneration. In the peripheral nervous system, Schwann cells (SCs) and macrophages, under the control of a network of cytokines and chemokines, represent the main cell...
In the peripheral nervous system, Schwann cells make myelin, a specialized sheath that is essential for rapid axonal conduction of action potentials. Immature Schwann cells initially interact with many axons, but, through a process termed radial sorting, eventually interact with one segment of a single axon as promyelinating Schwann cells. Previous studies have identified genes that are required for...
Myelin biogenesis is a complex process involving coordinated exocytosis, endocytosis, mRNA transport, and cytoskeletal dynamics. Although abnormalities of myelin are common in lysosomal storage diseases, our understanding of the role of lysosomes in the formation and maintenance of myelin is still limited. Here, we show that late endosomes/lysosomes in Schwann cells contain abundant myelin protein...
Myelin sheath thickness is precisely adjusted to axon caliber, and in the peripheral nervous system, neuregulin 1 (NRG1) type III is a key regulator of this process. It has been proposed that the protease BACE1 activates NRG1 dependent myelination. Here, we characterize the predicted product of BACE1‐mediated NRG1 type III processing in transgenic mice. Neuronal overexpression of a NRG1 type III‐variant,...
Both the central and the peripheral nervous systems are prone to multiple age‐dependent neurological deficits, often attributed to still unknown alterations in the function of myelinating glia. To uncover the biological processes affected in glial cells by aging, we analyzed gene expression of the Schwann cell‐rich mouse sciatic nerve at 17 time points throughout life, from day of birth until senescence...
Missense mutations affecting the LITAF gene (also known as SIMPLE) lead to the dominantly inherited peripheral neuropathy Charcot‐Marie‐Tooth disease type 1C (CMT1C). In this study, we sought to determine the requirement of Litaf function in peripheral nerves, the only known affected tissue in CMT1C. We reasoned that this knowledge is a prerequisite for a thorough understanding of the underlying disease...
Cerebroside sulfotransferase (CST) catalyzes the production of sulfatide, which is one of the major glycolipids in myelin. Homozygous CST knockout mice were shown to be completely deficient in sulfatide. They were born healthy but began to display progressive neurological deficits from 6 weeks of age. Severe abnormalities of paranodal regions and changes in axonal ion channel distribution were prominent...
Upon peripheral nerve injury, specific molecular events, including increases in the expression of selected neurotrophic factors, are initiated to prepare the tissue for regeneration. However, the mechanisms underlying these events and the nature of the cells involved are poorly understood. We used the injury‐induced upregulation of glial cell‐derived neurotrophic factor (GDNF) expression as a tool...
Rapid nerve conduction in jawed vertebrates is facilitated by the myelination of axons, which evolved in ancient cartilaginous fish. We aim to understand the coevolution of myelin and the major myelin proteins. We found that myelin basic protein (MBP) derived from living cartilaginous fish (sharks and rays) associated with the plasma membrane of glial cells similar to the phosphatidylinositol (4,5)‐bisphosphate...
Vestibular schwannomas (VSs) arise from Schwann cells (SCs) and result from the loss of function of merlin, the protein product of the NF2 tumor suppressor gene. In contrast to non‐neoplastic SCs, VS cells survive long‐term in the absence of axons. We find that p75NTR is overexpressed in VSs compared with normal nerves, both at the transcript and protein level, similar to the response of non‐neoplastic...
Axonal regeneration in the peripheral nervous system is greatly supported by Schwann cells (SCs). After nerve injury, SCs dedifferentiate to a progenitor‐like state and efficiently guide axons to their original target tissues. Contact and soluble factors participate in the crosstalk between SCs and axons during axonal regeneration. Here we show that dedifferentiated SCs secrete nano‐vesicles known...
Extracellular purines elicit strong signals in the nervous system. Adenosine‐5′‐triphosphate (ATP) does not spontaneously cross the plasma membrane, and nervous cells secrete ATP by exocytosis or through plasma membrane proteins such as connexin hemichannels. Using a combination of imaging, luminescence and electrophysiological techniques, we explored the possibility that Connexin 32 (Cx32), expressed...
Schwann cell (SC) migration is an important step preceding myelination and remyelination in the peripheral nervous system, and can be promoted by peptide factors like neuregulins. Here we present evidence that a lipid factor, lysophosphatidic acid (LPA), influences both SC migration and peripheral myelination through its cognate G protein‐coupled receptor (GPCR) known as LPA1. Ultrastructural analyses...
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