Schwann Cells: Neuroglial cells of the peripheral nervous system which form the insulating myelin sheaths of peripheral axons.Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the TIBIAL NERVE and the PERONEAL NERVE.Nerve Growth Factors: Factors which enhance the growth potentialities of sensory and sympathetic nerve cells.Receptors, Nerve Growth Factor: Cell surface receptors that bind NERVE GROWTH FACTOR; (NGF) and a NGF-related family of neurotrophic factors that includes neurotrophins, BRAIN-DERIVED NEUROTROPHIC FACTOR and CILIARY NEUROTROPHIC FACTOR.Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium.Muscle Denervation: The resection or removal of the innervation of a muscle or muscle tissue.Nerve Growth Factor: NERVE GROWTH FACTOR is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity.Plasmalogens: GLYCEROPHOSPHOLIPIDS in which one of the two acyl chains is attached to glycerol with an ether alkenyl linkage instead of an ester as with the other glycerophospholipids.Chondrodysplasia Punctata, Rhizomelic: An autosomal recessive form of CHONDRODYSPLASIA PUNCTATA characterized by defective plasmalogen biosynthesis and impaired peroxisomes. Patients have shortened proximal limbs and severely disturbed endochondral bone formation. The metabolic defects associated with the impaired peroxisomes are present only in the rhizomelic form of chondrodysplasia punctata. (From Scriver et al, Metabolic Basis of Inherited Disease, 6th ed, p1497)Chondrodysplasia Punctata: A heterogeneous group of bone dysplasias, the common character of which is stippling of the epiphyses in infancy. The group includes a severe autosomal recessive form (CHONDRODYSPLASIA PUNCTATA, RHIZOMELIC), an autosomal dominant form (Conradi-Hunermann syndrome), and a milder X-linked form. Metabolic defects associated with impaired peroxisomes are present only in the rhizomelic form.Myelin Sheath: The lipid-rich sheath surrounding AXONS in both the CENTRAL NERVOUS SYSTEMS and PERIPHERAL NERVOUS SYSTEM. The myelin sheath is an electrical insulator and allows faster and more energetically efficient conduction of impulses. The sheath is formed by the cell membranes of glial cells (SCHWANN CELLS in the peripheral and OLIGODENDROGLIA in the central nervous system). Deterioration of the sheath in DEMYELINATING DISEASES is a serious clinical problem.Glycogen Synthase Kinase 3: A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.Phytanic Acid: A 20-carbon branched chain fatty acid. In phytanic acid storage disease (REFSUM DISEASE) this lipid may comprise as much as 30% of the total fatty acids of the plasma. This is due to a phytanic acid alpha-hydroxylase deficiency.Neuregulin-1: A peptide factor originally identified by its ability to stimulate the phosphorylation the erbB-2 receptor (RECEPTOR, ERBB-2). It is a ligand for the erbB-3 receptor (RECEPTOR, ERBB-3) and the erbB-4 receptor. Variant forms of NEUREGULIN-1 occur through alternative splicing of its mRNA.Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.Ganglia, Spinal: Sensory ganglia located on the dorsal spinal roots within the vertebral column. The spinal ganglion cells are pseudounipolar. The single primary branch bifurcates sending a peripheral process to carry sensory information from the periphery and a central branch which relays that information to the spinal cord or brain.Antithrombin III Deficiency: An absence or reduced level of Antithrombin III leading to an increased risk for thrombosis.Spinal Cord Injuries: Penetrating and non-penetrating injuries to the spinal cord resulting from traumatic external forces (e.g., WOUNDS, GUNSHOT; WHIPLASH INJURIES; etc.).Spinal Cord: A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.Leprosy: A chronic granulomatous infection caused by MYCOBACTERIUM LEPRAE. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid.Transplantation, Autologous: Transplantation of an individual's own tissue from one site to another site.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Hematopoietic Stem Cell Transplantation: Transfer of HEMATOPOIETIC STEM CELLS from BONE MARROW or BLOOD between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). Hematopoietic stem cell transplantation has been used as an alternative to BONE MARROW TRANSPLANTATION in the treatment of a variety of neoplasms.Friedreich Ataxia: An autosomal recessive disease, usually of childhood onset, characterized pathologically by degeneration of the spinocerebellar tracts, posterior columns, and to a lesser extent the corticospinal tracts. Clinical manifestations include GAIT ATAXIA, pes cavus, speech impairment, lateral curvature of spine, rhythmic head tremor, kyphoscoliosis, congestive heart failure (secondary to a cardiomyopathy), and lower extremity weakness. Most forms of this condition are associated with a mutation in a gene on chromosome 9, at band q13, which codes for the mitochondrial protein frataxin. (From Adams et al., Principles of Neurology, 6th ed, p1081; N Engl J Med 1996 Oct 17;335(16):1169-75) The severity of Friedreich ataxia associated with expansion of GAA repeats in the first intron of the frataxin gene correlates with the number of trinucleotide repeats. (From Durr et al, N Engl J Med 1996 Oct 17;335(16):1169-75)Iron-Binding Proteins: Proteins that specifically bind to IRON.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Iron: A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN.Sinorhizobium: A genus of gram-negative, aerobic, nonsporeforming rods which usually contain granules of poly-beta-hydroxybutyrate. (From Bergey's Manual of Determinative Bacteriology, 9th ed)rac GTP-Binding Proteins: A sub-family of RHO GTP-BINDING PROTEINS that is involved in regulating the organization of cytoskeletal filaments. This enzyme was formerly listed as EC The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Oligodendroglia: A class of large neuroglial (macroglial) cells in the central nervous system. Oligodendroglia may be called interfascicular, perivascular, or perineuronal (not the same as SATELLITE CELLS, PERINEURONAL of GANGLIA) according to their location. They form the insulating MYELIN SHEATH of axons in the central nervous system.Nerve Regeneration: Renewal or physiological repair of damaged nerve tissue.Peripheral Nerve Injuries: Injuries to the PERIPHERAL NERVES.Nerve Crush: Treatment of muscles and nerves under pressure as a result of crush injuries.Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.Neural Crest: The two longitudinal ridges along the PRIMITIVE STREAK appearing near the end of GASTRULATION during development of nervous system (NEURULATION). The ridges are formed by folding of NEURAL PLATE. Between the ridges is a neural groove which deepens as the fold become elevated. When the folds meet at midline, the groove becomes a closed tube, the NEURAL TUBE.Political Systems: The units based on political theory and chosen by countries under which their governmental power is organized and administered to their citizens.Myelin Proteins: MYELIN-specific proteins that play a structural or regulatory role in the genesis and maintenance of the lamellar MYELIN SHEATH structure.POU Domain Factors: A family of transcription factors characterized by the presence of a bipartite DNA-binding domain known as the POU domain. The POU domain contains two subdomains, a POU-specific domain and a POU-homeodomain. The POU domain was originally identified as a region of approximately 150 amino acids shared between the Pit-1, Oct-1, Oct-2, and Unc-86 transcription factors.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.

Confocal calcium imaging reveals an ionotropic P2 nucleotide receptor in the paranodal membrane of rat Schwann cells. (1/1583)

1. The paranodal Schwann cell region is of major importance for the function of a myelinated axon. In the present study we searched for a possible ionotropic effect of extracellular ATP in this Schwann cell compartment. 2. Whole-cell patch-clamp recordings from cultured rat Schwann cells revealed that ATP and 2'-3'-O-(4-benzoylbenzoyl)-adenosine 5'-triphosphate (BzATP) induced a non-specific cation current. The effect of ATP was much enhanced in a Ca2+- and Mg2+-free solution. ADP, UTP and alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-meATP) had no effect. 3. Confocal Ca2+ imaging of myelinating Schwann cells in isolated rat spinal roots showed a BzATP-induced rise in the free intracellular Ca2+ concentration in the paranodal Schwann cell cytoplasm whereas alpha,beta-meATP and 2-(methylthio)-adenosine 5'-triphosphate were without effect. In contrast to the known metabotropic effect of UTP on these Schwann cell regions, the BzATP-induced Ca2+ signal was not transient, was unaffected by depletion of intracellular Ca2+ stores and dependent on the presence of extracellular Ca2+. 4. These results suggest that an ionotropic ATP receptor with electrophysiological and pharmacological characteristics of the P2X7 subtype of nucleotide receptors is functionally active in myelinating Schwann cells of peripheral nerves. Such a receptor might contribute to Schwann cell reactions in nerve injury or neuropathy.  (+info)

Transport of Trembler-J mutant peripheral myelin protein 22 is blocked in the intermediate compartment and affects the transport of the wild-type protein by direct interaction. (2/1583)

Peripheral myelin protein 22 (PMP22) is an integral membrane protein that is essential for the normal formation and maintenance of peripheral myelin. Duplications, deletions, or mutations in the PMP22 gene account for a set of dominantly inherited peripheral neuropathies. The heterozygous Trembler-J (TrJ) genotype in mice is similar genetically to a Charcot-Marie-Tooth disease type 1A pedigree in humans, whereas the homozygous TrJ condition leads to the most severe form of PMP22-associated neuropathies. To characterize the consequences of the TrJ mutation, we labeled wild-type (wt-) and TrJ-PMP22 in the third loop of the protein with different epitope tags and expressed them separately or together in COS7 cells and primary Schwann cells. Here we show that the transport of the mutant TrJ-PMP22 is interrupted in the intermediate compartment, preventing its insertion into the plasma membrane and affecting the morphology of the endoplasmic reticulum. In addition, TrJ-PMP22 forms a heterodimer with the wt-PMP22. This interaction causes a fraction of the wt-PMP22 to be retained with TrJ-PMP22 in the intermediate compartment of COS7 and Schwann cells. The relative stability of a wt-mutant PMP22 heterodimer as compared with the wt-wt PMP22 homodimer may determine whether a particular mutation is semidominant or dominant. The neuropathy itself appears to result both from decreased trafficking of wt-PMP22 to the plasma membrane and from a toxic gain of function via the accumulation of wt- and TrJ-PMP22 in the intermediate compartment.  (+info)

A role for insulin-like growth factor-I in the regulation of Schwann cell survival. (3/1583)

During postnatal development in the peripheral nerve, differentiating Schwann cells are susceptible to apoptotic death. Schwann cell apoptosis is regulated by axons and serves as one mechanism through which axon and Schwann cell numbers are correctly matched. This regulation is mediated in part by the provision of limiting axon-derived trophic molecules, although neuregulin-1 (NRG-1) is the only trophic factor shown to date to support Schwann cell survival. In this report, we identify insulin-like growth factor-I (IGF-I) as an additional trophin that can promote Schwann cell survival in vitro. We find that IGF-I, like NRG-1, can prevent the apoptotic death of postnatal rat Schwann cells cultured under conditions of serum withdrawal. Moreover, we show that differentiating Schwann cells in the rat sciatic nerve express both the IGF-I receptor (IGF-I R) and IGF-I throughout postnatal development. These results indicate that IGF-I is likely to control Schwann cell viability in the developing peripheral nerve and, together with other findings, raise the interesting possibility that such survival regulation may switch during postnatal development from an axon-dependent mechanism to an autocrine and/or paracrine one.  (+info)

A glial cell line-derived neurotrophic factor-secreting clone of the Schwann cell line SCTM41 enhances survival and fiber outgrowth from embryonic nigral neurons grafted to the striatum and to the lesioned substantia nigra. (4/1583)

We have developed a novel Schwann cell line, SCTM41, derived from postnatal sciatic nerve cultures and have stably transfected a clone with a rat glial cell line-derived neurotrophic factor (GDNF) construct. Coculture with this GDNF-secreting clone enhances in vitro survival and fiber growth of embryonic dopaminergic neurons. In the rat unilateral 6-OHDA lesion model of Parkinson's disease, we have therefore made cografts of these cells with embryonic day 14 ventral mesencephalic grafts and assayed for effects on dopaminergic cell survival and process outgrowth. We show that cografts of GDNF-secreting Schwann cell lines improve the survival of intrastriatal embryonic dopaminergic neuronal grafts and improve neurite outgrowth into the host neuropil but have no additional effect on amphetamine-induced rotation. We next looked to see whether bridge grafts of GDNF-secreting SCTM41 cells would promote the growth of axons to their striatal targets from dopaminergic neurons implanted orthotopically into the 6-OHDA-lesioned substantia nigra. We show that such bridge grafts increase the survival of implanted embryonic dopaminergic neurons and promote the growth of axons through the grafts to the striatum.  (+info)

Krox-20 controls SCIP expression, cell cycle exit and susceptibility to apoptosis in developing myelinating Schwann cells. (5/1583)

The transcription factors Krox-20 and SCIP each play important roles in the differentiation of Schwann cells. However, the genes encoding these two proteins exhibit distinct time courses of expression and yield distinct cellular phenotypes upon mutation. SCIP is expressed prior to the initial appearance of Krox-20, and is transient in both the myelinating and non-myelinating Schwann cell lineages; while in contrast, Krox-20 appears approximately 24 hours after SCIP and then only within the myelinating lineage, where its expression is stably maintained into adulthood. Similarly, differentiation of SCIP-/- Schwann cells appears to transiently stall at the promyelinating stage that precedes myelination, whereas Krox-20(-/-) cells are, by morphological criteria, arrested at this stage. These observations led us to examine SCIP regulation and Schwann cell phenotype in Krox-20 mouse mutants. We find that in Krox-20(-/-) Schwann cells, SCIP expression is converted from transient to sustained. We further observe that both Schwann cell proliferation and apoptosis, which are normal features of SCIP+ cells, are also markedly increased late in postnatal development in Krox-20 mutants relative to wild type, and that the levels of cell division and apoptosis are balanced to yield a stable number of Schwann cells within peripheral nerves. These data demonstrate that the loss of Krox-20 in myelinating Schwann cells arrests differentiation at the promyelinating stage, as assessed by SCIP expression, mitotic activity and susceptibility to apoptosis.  (+info)

Characterization of the transmembrane molecular architecture of the dystroglycan complex in schwann cells. (6/1583)

We have demonstrated previously 1) that the dystroglycan complex, but not the sarcoglycan complex, is expressed in peripheral nerve, and 2) that alpha-dystroglycan is an extracellular laminin-2-binding protein anchored to beta-dystroglycan in the Schwann cell membrane. In the present study, we investigated the transmembrane molecular architecture of the dystroglycan complex in Schwann cells. The cytoplasmic domain of beta-dystroglycan was co-localized with Dp116, the Schwann cell-specific isoform of dystrophin, in the abaxonal Schwann cell cytoplasm adjacent to the outer membrane. beta-dystroglycan bound to Dp116 mainly via the 15 C-terminal amino acids of its cytoplasmic domain, but these amino acids were not solely responsible for the interaction of these two proteins. Interestingly, the beta-dystroglycan-precipitating antibody precipitated only a small fraction of alpha-dystroglycan and did not precipitate laminin and Dp116 from the peripheral nerve extracts. Our results indicate 1) that Dp116 is a component of the submembranous cytoskeletal system that anchors the dystroglycan complex in Schwann cells, and 2) that the dystroglycan complex in Schwann cells is fragile compared with that in striated muscle cells. We propose that this fragility may be attributable to the absence of the sarcoglycan complex in Schwann cells.  (+info)

Neural cell surface differentiation antigen gp130(RB13-6) induces fibroblasts and glioma cells to express astroglial proteins and invasive properties. (7/1583)

Transient expression of the differentiation and tumor cell surface antigen gp130(RB13-6) characterizes a subset of rat glial progenitor cells susceptible to ethylnitrosourea-induced neurooncogenesis. gp130(RB13-6) is as a member of an emerging protein family of ecto-phosphodiesterases/nucleotide pyrophosphatases that includes PC-1 and the tumor cell motility factor autotaxin. We have investigated the potential role of gp130(RB13-6) in glial differentiation by transfection of three cell lines of different origin that do not express endogenous gp130(RB13-6) (NIH-3T3 mouse fibroblasts; C6 and BT7Ca rat glioma cells) with the cDNA encoding gp130(RB13-6). The effect of gp130(RB13-6) expression was analyzed in terms of overall cell morphology, the expression of glial cell-specific marker proteins, and invasiveness. Transfectant sublines, consisting of 100% gp130(RB13-6)-positive cells, exhibited an altered, bipolar morphology. Fascicular aggregates of fibroblastoid cells subsequently developed into mesh-like patterns. Contrary to the parental NIH-3T3 and BT7Ca cells, the transfectant cells invaded into collagen type I. As shown by immunofluorescence staining of the transfectant sublines as well as of primary cultures composed of gp130(RB13-6)-positive and -negative cells, expression of gp130(RB13-6) induced coexpression of proteins typical for glial cells and their precursors, i.e., glial fibrillary acidic protein, the low affinity nerve growth factor receptor, and the neural proteins Thy-1, Ran-2, and S-100. In accordance with its expression in the immature rat nervous system, gp130(RB13-6) may thus have a significant role in the glial differentiation program and its subversion in neurooncogenesis.  (+info)

Schwann cell hyperplasia and tumors in transgenic mice expressing a naturally occurring mutant NF2 protein. (8/1583)

Specific mutations in some tumor suppressor genes such as p53 can act in a dominant fashion. We tested whether this mechanism may also apply for the neurofibromatosis type-2 gene (NF2) which, when mutated, leads to schwannoma development. Transgenic mice were generated that express, in Schwann cells, mutant NF2 proteins prototypic of natural mutants observed in humans. Mice expressing a NF2 protein with an interstitial deletion in the amino-terminal domain showed high prevalence of Schwann cell-derived tumors and Schwann cell hyperplasia, whereas those expressing a carboxy-terminally truncated protein were normal. Our results indicate that a subset of mutant NF2 alleles observed in patients may encode products with dominant properties when overexpressed in specific cell lineages.  (+info)

  • In contrast to neurons, where pp140trk appears to be the functionally critical NGF receptor, NGF responses in Schwann cells depend on LNGFR. (
  • In studies of contusion SCI in the rat using mitogen-expanded cells, we have shown that SC transplantation at seven days after injury significantly fosters axon regeneration and myelination, improves host tissue preservation, 4 and reduces cavitation 4,14 in a thoracic SCI paradigm and increases numbers of preserved NeuN positive neurons rostral and caudal to the injury/graft site 17 after cervical SCI. (
  • We have investigated the potential regulatory role of TGF-beta in the interactions of neurons and Schwann cells using an in vitro myelinating system. (
  • Addition of TGF-beta 1 to the cocultures inhibits many of the effects of the axon on Schwann cells, antagonizing the proliferation induced by contact with neurons, and, strikingly, blocking myelination. (
  • These effects of TGF-beta 1 on Schwann cell differentiation are likely to be direct effects on the Schwann cells themselves which express high levels of TGF-beta 1 receptors when cocultured with neurons. (
  • In the process of peripheral nerve repair and regeneration, Schwann cells are crucial factors that clear up cell residue due to their phagocytic function, providing neurons with nutritional factors and suitable space[ 4 ]. (
  • Co-cultures with stem cell-derived human sensory neurons reveal regulators of peripheral myelination. (
  • We have established conditions by which human induced pluripotent stem cell-derived sensory neurons can be cultured with rat Schwann cells, and have produced for the first time long-term and stable myelinating co-cultures with human neurons. (
  • Expression of type III neuregulin-1 (TIIINRG1) in induced pluripotent stem cell-derived sensory neurons strongly enhances myelination, while conversely pharmacological blockade of the NRG1-ErbB pathway prevents myelination, providing direct evidence for the ability of this pathway to promote the myelination of human sensory axons. (
  • Myelinating co-cultures using human induced pluripotent stem cell-derived sensory neurons thus provide insights into the cellular and molecular specialization of axoglial signalling, how pharmacological agents may promote or impede such signalling and the pathogenic effects of ganglioside antibodies.awx012media15372351982001. (
  • Schwann cells (SCs), glial cells normally present in peripheral nerve, are responsible for axon regeneration after nerve injury. (
  • Transforming growth factor-beta 1 regulates axon/Schwann cell interactions. (
  • Expression of TGF-beta 1, a major isoform produced by Schwann cells, is specifically and significantly downregulated as a result of axon/Schwann cell interactions. (
  • We saw a set of latent genes becoming active, but only after injury," says Svaren, "and these started a program that places the Schwann cells in a repair mode where they perform several jobs that the axon needs to regrow. (
  • The Schwann cells also secrete signals that summon blood cells to aid the cleanup, and they map out a pathway for the axon to regrow. (
  • Supportive Schwann cells (green) surround the conductive axon (purple) of a neuron in the peripheral nervous system in this artificially colored image. (
  • A new study by John Svaren shows that Schwann cells not only make the insulating myelin (black), but also are active players in axon repair after damage. (
  • Migrating Schwann cells in developing or regenerating peripheral nerves are known to express dramatically increased levels of nerve growth factor (NGF) and the low-affinity NGF receptor (LNGFR). (
  • (
  • Results show that Schwann cells migrate more rapidly on denervated than on normal sciatic nerve. (
  • Pretreatment of denervated nerve sections with NGF increases further the rate of Schwann cell migration. (
  • Large numbers of autologous human SCs (ahSCs) can be obtained for implantation after a peripheral nerve biopsy followed by dissociation and expansion of their cell numbers in culture with mitogens. (
  • Large numbers of ahSC can be derived for autologous implantation after a minor surgery for peripheral nerve harvesting, and purification and expansion of the cells in culture. (
  • They have also been largely responsible for developing an efficient method for procuring large, essentially pure populations of human Schwann cells from adult peripheral nerve. (
  • Schwann cells harvested from the sural nerve of the participant will be autologously transplanted into the epicenter of the participant's spinal cord injury. (
  • Previous work demonstrated that Schwann cells (SCs) must interact with nerve cells (NCs) in order to generate their basal lamina (BL) in culture (M. B. Bunge, A. K. Williams, and P. M. Wood, 1982, Dev. (
  • During peripheral nerve myelination, Schwann cells sort larger axons, ensheath them, and eventually wrap their membrane to form the myelin sheath. (
  • During development, TGF-beta 1 could serve as an inhibitor of Schwann cell proliferation and myelination, whereas after peripheral nerve injury, it may promote the transition of Schwann cells to a proliferating, nonmyelinating phenotype, and thereby enhance the regenerative response. (
  • The participants will undergo a biopsy of a sensory nerve in one leg to obtain the tissue from which to grow their own Schwann cells. (
  • Schwann cells are the myelinating glial cells of the peripheral nervous system and exert important regenerative functions revealing them as central repair components of many peripheral nerve pathologies. (
  • We therefore examined whether immunoglobulins affect glial cell homeostasis, differentiation, and Schwann cell dependent nerve regenerative processes. (
  • This immune competence along with the plastic differentiation potential of Schwann cells provide the PNS with a certain regeneration capacity and further indicates that these glial cells are central components of many, if not all, nerve pathologies. (
  • Purified Schwann cells were cultured from neonatal rat sciatic nerve using a modification of the method of Brockes (Brockes, J.P. et al, Brain Res. (
  • Recently, Schwann cells were recognized in the repair of the peripheral nerve system, including cell migration, viability, proliferation, and nutritional factor secretion activity[ 5 ]. (
  • Schwann cells create the insulating myelin sheath that speeds transmission of nerve impulses. (
  • In the repair mode, Schwann cells form a fix-up crew that adds house cleaning and stimulation of nerve regrowth to the usual insulating job. (
  • After the human genome was deciphered, epigenetics - the study of gene regulation - has moved to the forefront with the realization that genes don't matter much until they are switched on, and that genetic switches are the fundamental reason why a skin cell doesn't look like a nerve cell, and a nerve cells functions differently than a white blood cell. (
  • See Saporta and Shy (doi:10.1093/awx048) for a scientific commentary on this article.Effective bidirectional signalling between axons and Schwann cells is essential for both the development and maintenance of peripheral nerve function. (
  • An immunoprecipitation technique was used to detect radiolabeled peptides in a nonionic detergent extract of freshly prepared, surface‐radioiodinated Schwann cells that were bound by a rabbit anti‐Schwann cell serum preabsorbed with rat fibroblasts. (
  • Schwann cells and contaminating fibroblasts were unambiguously identified using fluorescent antibodies to 2'3' cyclic nucleotide 3'-phosphodiesterase and the thy 1.1 antigen respectively. (
  • In the case of purified Schwann cells, treatment with TGF-beta 1 increases their proliferation, and it promotes a pre- or nonmyelinating Schwann cell phenotype characterized by increased NCAM expression, decreased NGF receptor expression, inhibition of the forskolin-mediated induction of the myelin protein P0, and induction of the Schwann cell transcription factor suppressed cAMP-inducible POU protein. (
  • Loss of function of merlin encoded by the NF2 tumor suppressor gene leads to activation of multiple mitogenic signaling cascades, including platelet-derived growth factor receptor (PDGFR) and SRC in Schwann cells. (
  • We generated a conditional knock-out mouse in which the type II TGF beta receptor is specifically ablated only in Schwann cells. (
  • Inactivation of the receptor, evident at least from embryonic day 18, resulted in suppressed Schwann cell death in normally developing and injured nerves. (
  • This is the first in vivo evidence for a growth factor receptor involved in promoting Schwann cell division during development and the first genetic evidence for a receptor that controls normal developmental Schwann cell death. (
  • We found that IVIG specifically bind to Schwann cells and detected CD64 Fc receptor expression on their surface. (
  • In the injured PNS, a repair response is initiated by Schwann cells in which they degrade and phagocytose extracellular myelin debris, attract macrophages for further clearance, and provide axons a supportive and attractive environment to grow along [ 2 , 3 ]. (
  • In the peripheral nervous system, Schwann cells (SCs) and macrophages, under the control of a network of cytokines and chemokines, represent the main cell types involved in this process. (
  • In the lesion milieu, transplanted SCs may be effective through their production of growth promoting trophic molecules, 7 their deposition of matrix molecules collagen and laminin into the extracellular space, 8 as well as their expression of surface membrane cell adhesion molecules such as NCAM and L1. (
  • The regulated expression of TGF-beta 1 and its effects on Schwann cells suggest that it may be an important autocrine and paracrine mediator of neuron/Schwann cell interactions. (
  • Schwann cells were separated from new natal Sprague-Dawley rat sciatic nerves and were cultured and purified. (
  • These results suggest that one function of the elevated levels of NGF known to be present in embryonic and regenerating peripheral nerves is to promote the migration of Schwann cells. (
  • Microglial cells begin to invade the cortex at 11.5 days of embryonic age (E11.5). (
  • Time-lapse analysis shows that embryonic microglia are highly dynamic cells. (
  • Almost every other nervous-system injury response, especially in the brain, is thought to require stem cells to repopulate the cells, but there are no stem cells here," Svaren says. (
  • These data suggest that regulation of actin filament nucleation in Schwann cells by N-WASP is crucial for membrane wrapping, longitudinal extension, and myelination. (
  • The Schwann cells were quiescent unless challenged with mitogens, They proliferated rapidly in response to the soluable mitogen, cholera toxin, or to membrane fractions from rat CNS or PNS, prepared by the method of DeVries (DeVries, G.H., J Neurochem, 40 (1983) 1709-1717). (
  • The Journal of Cell Biology , 192 (2), 243-250. (
  • Led by W. Dalton Dietrich, Ph.D. , Scientific Director of The Miami Project and Professor of Neurological Surgery, Neurology and Cell Biology & Anatomy, the Schwann cell clinical trial team at The Miami Project is composed of a multi-disciplinary group of basic science and clinical faculty members, scientific staff, and regulatory personnel focused on advancing the trial. (
  • 23 Autologous cells in general offer important safety advantages over allogeneic sources that include minimal risk of disease transfer, low risk of tumorigenicity, and the absence of immunosuppressive medication requirements. (
  • Autologous cells offer important safety advantages that include no need for immune suppression, minimal risk of disease transfer, and a low risk of tumorigenicity. (
  • The molecular mechanisms that regulate Schwann cell (SC) plasticity and the role of the Nrg1/ErbB-induced MEK1/ERK1/2 signalling pathway in SC dedifferentiation or in myelination remain unclear. (
  • In N-WASP-deficient nerves, Schwann cells sort and ensheath axons, but most of them fail to myelinate and arrest at the promyelinating stage. (
  • Arf1 is a small guanosine triphosphate-binding protein that plays multiple roles in intracellular trafficking and related signaling, both of which are processes involved in cell morphogenesis. (
  • Low-intensity pulsed ultrasound (LIPUS) has been reported to enhance proliferation and alter protein production in various types of cells. (
  • In this perspective, we have investigated the potential role of KIAA1199, a protein that promotes ErbB and MEK1/ERK1/2 signalling in cancer cells, in SC plasticity. (
  • In the repair mode, but not in the normal one, Schwann cells start cleaning house, helping to dissolve myelin, which is essential for proper functioning but ironically deters regeneration after injury. (
  • Svaren, senior author of a report published Aug. 30 in The Journal of Neuroscience , studied how Schwann cells, which hug axons in the peripheral nervous system, transform themselves to play a much more active and "intelligent" role after injury. (
  • When designing a Phase I trial involving the surgical delivery of cells into the spinal cord parenchyma during the first few months after injury, however, risk must be mitigated as much as possible. (
  • This trial, when completed successfully, will lay the critical foundation for future cell-based therapies to target spinal cord injuries. (