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Remyelination

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https://www.readbyqxmd.com/read/28210970/a-suspended-carbon-fiber-culture-to-model-myelination-by-human-schwann-cells
#1
Antonio Merolli, Yong Mao, Joachim Kohn
Understanding of myelination/remyelination process is essential to guide tissue engineering for nerve regeneration. In vitro models currently used are limited to cell population studies and cannot easily identify individual cell contribution to the process. We established a novel model to study the contribution of human Schwann cells to the myelination process. The model avoids the presence of neurons in culture; Schwann cells respond solely to the biophysical properties of an artificial axon. The model uses a single carbon fiber suspended in culture media far from the floor of the well...
April 2017: Journal of Materials Science. Materials in Medicine
https://www.readbyqxmd.com/read/28206686/nte-pnpla6-is-expressed-in-mature-schwann-cells-and-is-required-for-glial-ensheathment-of-remak-fibers
#2
Janis McFerrin, Bruce L Patton, Elizabeth R Sunderhaus, Doris Kretzschmar
Neuropathy target esterase (NTE) or patatin-like phospholipase domain containing 6 (PNPLA6) was first linked with a neuropathy occurring after organophosphate poisoning and was later also found to cause complex syndromes when mutated, which can include mental retardation, spastic paraplegia, ataxia, and blindness. NTE/PNPLA6 is widely expressed in neurons but experiments with its Drosophila orthologue Swiss-cheese (SWS) suggested that it may also have glial functions. Investigating whether NTE/PNPLA6 is expressed in glia, we found that NTE/PNPLA6 is expressed by Schwann cells in the sciatic nerve of adult mice with the most prominent expression in nonmyelinating Schwann cells...
February 16, 2017: Glia
https://www.readbyqxmd.com/read/28203609/zeb2-inhibiting-the-inhibitors-in-schwann-cells
#3
Bastian G Brinkmann, Susanne Quintes
Development of Schwann cells is tightly regulated by concerted action of activating and inhibiting factors. Most of the regulatory feedback loops identified to date are transcriptional activators promoting induction of genes coding for integral myelin proteins and lipids. The mechanisms by which inhibitory factors are silenced during Schwann cell maturation are less well understood. We could recently show a pivotal function for the transcription factor zinc finger E-box binding homeobox 2 (Zeb2) during Schwann cell development and myelination as a transcriptional repressor of maturation inhibitors...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28203606/dna-methylation-in-oligodendroglial-cells-during-developmental-myelination-and-in-disease
#4
Sarah Moyon, Patrizia Casaccia
Oligodendrocyte progenitor cells (OPC) are the myelinating cells of the central nervous system (CNS). During development, they differentiate into mature oligodendrocytes (OL) and ensheath axons, providing trophic and functional support to the neurons. This process is regulated by the dynamic expression of specific transcription factors, which, in turn, is controlled by epigenetic marks such as DNA methylation. Here we discuss recent findings showing that DNA methylation levels are differentially regulated in the oligodendrocyte lineage during developmental myelination, affecting both genes expression and alternative splicing events...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28193690/lingo-1-regulates-oligodendrocyte-differentiation-through-the-cytoplasmic-gelsolin-signaling-pathway
#5
Zhaohui Shao, Xinhua Lee, Guanrong Huang, Guoqing Sheng, Christopher E Henderson, Daniel Louvard, Jiho Sohn, Blake Pepinsky, Sha Mi
Differentiation and maturation of oligodendrocyte progenitor cells (OPCs) involve the assembly and disassembly of actin microfilaments. How actin dynamics is regulated during this process remains poorly understood. Leucine rich repeat and Immunoglobulin-like domain-containing Nogo receptor interacting protein 1(LINGO-1) is a negative regulator of OPC differentiation. We discovered that anti-LINGO-1 antibody promoted OPC differentiation was accompanied by upregulation of cytoplasmic gelsolin (cGSN), an abundant actin-severing protein involved in the depolymerization of actin filaments...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28191772/human-induced-pluripotent-cell-derived-sensory-neurons-for-fate-commitment-of-bone-marrow-derived-schwann-cells-implications-for-remyelination-therapy
#6
Sa Cai, Lei Han, Qiang Ao, Ying-Shing Chan, Daisy Kwok-Yan Shum
Strategies that exploit induced pluripotent stem cells (iPSCs) to derive neurons have relied on cocktails of cytokines and growth factors to bias cell-signaling events in the course of fate choice. These are often costly and inefficient, involving multiple steps. In this study, we took an alternative approach and selected 5 small-molecule inhibitors of key signaling pathways in an 8-day program to induce differentiation of human iPSCs into sensory neurons, reaching ≥80% yield in terms of marker proteins. Continuing culture in maintenance medium resulted in neuronal networks immunopositive for synaptic vesicle markers and vesicular glutamate transporters suggestive of excitatory neurotransmission...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28191764/neural-progenitor-like-cells-induced-from-human-gingiva-derived-mesenchymal-stem-cells-regulate-myelination-of-schwann-cells-in-rat-sciatic-nerve-regeneration
#7
Qunzhou Zhang, Phuong Nguyen, Qilin Xu, Wonse Park, Sumin Lee, Akihiro Furuhashi, Anh D Le
Regeneration of peripheral nerve injury remains a major clinical challenge. Recently, mesenchymal stem cells (MSCs) have been considered as potential candidates for peripheral nerve regeneration; however, the underlying mechanisms remain elusive. Here, we show that human gingiva-derived MSCs (GMSCs) could be directly induced into multipotent NPCs (iNPCs) under minimally manipulated conditions without the introduction of exogenous genes. Using a crush-injury model of rat sciatic nerve, we demonstrate that GMSCs transplanted to the injury site could differentiate into neuronal cells, whereas iNPCs could differentiate into both neuronal and Schwann cells...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28188715/-multiple-sclerosis-current-immunological-aspects
#8
Carlos Cuevas-García
Multiple sclerosis is the most common inflammatory, chronic and degenerative condition of the central nervous system, and represents the first cause of disability in young adults. In Mexico, 11 to 20 out of every 100 000 people suffer from this disease. The causes of multiple sclerosis remain unknown, but several theories have been proposed: the interaction of environmental factors, viral infectious factors and genetic and immune susceptibility of each individual patient, which induce an autoimmune response and promote neuronal/axonal degeneration...
January 2017: Revista Alergia Mexico: Organo Oficial de la Sociedad Mexicana de Alergia e Inmunología, A.C
https://www.readbyqxmd.com/read/28185662/alphab-crystallin-expression-correlates-with-aging-deficits-in-the-peripheral-nervous-system
#9
Erin-Mai F Lim, Alim Musa, Ariana Frederick, Shalina S Ousman
In an effort to identify factors that contribute to age-related deficits in the undamaged and injured peripheral nervous system (PNS), we noted that Brady and colleagues found that mice null for a small heat shock protein called alphaB-crystallin (αBC) developed abnormalities early in life that are reminiscent of aging pathologies. Because of our observation that αBC protein levels markedly reduce as wild-type mice age, we investigated whether the crystallin plays a role in modulating age-related deficits in the uninjured and damaged PNS...
January 12, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28161197/icariin-enhances-remyelination-process-after-acute-demyelination-induced-by-cuprizone-exposure
#10
Yifan Zhang, Linlin Yin, Na Zheng, Li Zhang, Jianghong Liu, Weixiong Liang, Qi Wang
Pathology are still progressive and cumulative in the remission course of relapsing-remitting MS (RRMS), thus drug treatment during the remission period may play a great role for the regeneration of the myelin sheath. C57BL/6 mice were fed with cuprizone (CPZ, 0.2% w/w) for 5 weeks to induce acute demyelination and oligodendrocytes degeneration, after which CPZ was withdrawn to allow recovery. Icariin (ICA, 6.25, 12.5 and 25mg/kg/day), vehicle (0.5% sodium carboxymethyl cellulose solution) or water was administrated orally to mice for 1 week after CPZ withdrawal...
February 1, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28153091/effect-of-fingolimod-on-neural-stem-cells-a-novel-mechanism-and-broadened-application-for-neural-repair
#11
Yuan Zhang, Xing Li, Bogoljub Ciric, Cun-Gen Ma, Bruno Gran, Abdolmohamad Rostami, Guang-Xian Zhang
Inflammatory demyelination and axonal damage of the CNS are hallmarks of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Fingolimod (FTY720), the first FDA-approved oral medication for MS, suppresses acute disease but is less effective at the chronic stage, and whether it has a direct effect on neuroregeneration in MS and EAE remains unclear. Here we show that FTY720, at nanomolar concentrations, effectively protected survival of neural stem cells (NSCs) and enhanced their development into mature oligodendrocytes (OLGs) in vitro, primarily through the S1P3 and S1P5 receptors...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28147220/intersections-of-pathways-involving-biotin-and-iron-relative-to-therapeutic-mechanisms-for-progressive-multiple-sclerosis
#12
Rebecca M Heidker, Mitchell R Emerson, Steven M LeVine
While there are a variety of therapies for relapsing remitting multiple sclerosis (MS), there is a lack of treatments for progressive MS. An early study indicated that high dose biotin therapy has beneficial effects in approximately 12-15% of patients with progressive MS. The mechanisms behind the putative improvements seen with biotin therapy are not well understood, but have been postulated to include: 1) improving mitochondrial function which is impaired in MS, 2) increasing synthesis of lipids and cholesterol to facilitate remyelination, and 3) affecting gene expression...
December 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28145507/transplanted-mir-219-overexpressing-oligodendrocyte-precursor-cells-promoted-remyelination-and-improved-functional-recovery-in-a-chronic-demyelinated-model
#13
Hong-Bin Fan, Li-Xia Chen, Xue-Bin Qu, Chuan-Lu Ren, Xiu-Xiang Wu, Fu-Xing Dong, Bao-Le Zhang, Dian-Shuai Gao, Rui-Qin Yao
Oligodendrocyte precursor cells (OPCs) have the ability to repair demyelinated lesions by maturing into myelin-producing oligodendrocytes. Recent evidence suggests that miR-219 helps regulate the differentiation of OPCs into oligodendrocytes. We performed oligodendrocyte differentiation studies using miR-219-overexpressing mouse embryonic stem cells (miR219-mESCs). The self-renewal and multiple differentiation properties of miR219-mESCs were analyzed by the expression of the stage-specific cell markers Nanog, Oct4, nestin, musashi1, GFAP, Tuj1 and O4...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28144983/human-olfactory-mesenchymal-stromal-cell-transplants-promote-remyelination-and-earlier-improvement-in-gait-co-ordination-after-spinal-cord-injury
#14
Susan L Lindsay, Andrew Toft, Jacob Griffin, Ahmed M M Emraja, Susan Carol Barnett, John S Riddell
Autologous cell transplantation is a promising strategy for repair of the injured spinal cord. Here we have studied the repair potential of mesenchymal stromal cells isolated from the human olfactory mucosa after transplantation into a rodent model of incomplete spinal cord injury. Investigation of peripheral type remyelination at the injury site using immunocytochemistry for P0, showed a more extensive distribution in transplanted compared with control animals. In addition to the typical distribution in the dorsal columns (common to all animals), in transplanted animals only, P0 immunolabelling was consistently detected in white matter lateral and ventral to the injury site...
February 1, 2017: Glia
https://www.readbyqxmd.com/read/28139683/delaying-histone-deacetylase-response-to-injury-accelerates-conversion-into-repair-schwann-cells-and-nerve-regeneration
#15
Valérie Brügger, Mert Duman, Maëlle Bochud, Emmanuelle Münger, Manfred Heller, Sophie Ruff, Claire Jacob
The peripheral nervous system (PNS) regenerates after injury. However, regeneration is often compromised in the case of large lesions, and the speed of axon reconnection to their target is critical for successful functional recovery. After injury, mature Schwann cells (SCs) convert into repair cells that foster axonal regrowth, and redifferentiate to rebuild myelin. These processes require the regulation of several transcription factors, but the driving mechanisms remain partially understood. Here we identify an early response to nerve injury controlled by histone deacetylase 2 (HDAC2), which coordinates the action of other chromatin-remodelling enzymes to induce the upregulation of Oct6, a key transcription factor for SC development...
January 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28137843/alphab-crystallin-regulates-remyelination-after-peripheral-nerve-injury
#16
Erin-Mai F Lim, Stan T Nakanishi, Vahid Hoghooghi, Shane E A Eaton, Alexandra L Palmer, Ariana Frederick, Jo A Stratton, Morgan G Stykel, Patrick J Whelan, Douglas W Zochodne, Jeffrey Biernaskie, Shalina S Ousman
AlphaB-crystallin (αBC) is a small heat shock protein that is constitutively expressed by peripheral nervous system (PNS) axons and Schwann cells. To determine what role this crystallin plays after peripheral nerve damage, we found that loss of αBC impaired remyelination, which correlated with a reduced presence of myelinating Schwann cells and increased numbers of nonmyelinating Schwann cells. The heat shock protein also seems to regulate the cross-talk between Schwann cells and axons, because expected changes in neuregulin levels and ErbB2 receptor expression after PNS injury were disrupted in the absence of αBC...
January 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28137778/merlin-controls-the-repair-capacity-of-schwann-cells-after-injury-by-regulating-hippo-yap-activity
#17
Thomas Mindos, Xin-Peng Dun, Katherine North, Robin D S Doddrell, Alexander Schulz, Philip Edwards, James Russell, Bethany Gray, Sheridan L Roberts, Aditya Shivane, Georgina Mortimer, Melissa Pirie, Nailing Zhang, Duojia Pan, Helen Morrison, David B Parkinson
Loss of the Merlin tumor suppressor and activation of the Hippo signaling pathway play major roles in the control of cell proliferation and tumorigenesis. We have identified completely novel roles for Merlin and the Hippo pathway effector Yes-associated protein (YAP) in the control of Schwann cell (SC) plasticity and peripheral nerve repair after injury. Injury to the peripheral nervous system (PNS) causes a dramatic shift in SC molecular phenotype and the generation of repair-competent SCs, which direct functional repair...
February 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28128996/endogenous-repair-and-development-inspired-therapy-of-neurodegeneration-in-progressive-multiple-sclerosis
#18
Ethan Hollingsworth, Jamil Khouri, Jaime Imitola
In recent years, there has been progress in understanding the etiology and immune mechanisms of multiple sclerosis (MS). However, for most, once the diagnosis is made, significant pathology is already present in the central nervous system (CNS), and in many, this leads to neurodegeneration, which accumulates in disability. Although, the mechanisms of such progression are poorly understood, new data suggest lack of remyelination paired with dysfunction of neurons along with stem and progenitor cells as the basis and recent developmental studies suggest that CNS repair processes share mechanisms with development...
January 27, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/28128219/astrocyte-derived-tissue-transglutaminase-affects-fibronectin-deposition-but-not-aggregation-during-cuprizone-induced-demyelination
#19
Nathaly Espitia Pinzon, Berta Sanz-Morello, John J P Brevé, John G J M Bol, Benjamin Drukarch, Jan Bauer, Wia Baron, Anne-Marie van Dam
Astrogliosis as seen in Multiple Sclerosis (MS) develops into astroglial scarring, which is beneficial because it seals off the site of central nervous system (CNS) damage. However, astroglial scarring also forms an obstacle that inhibits axon outgrowth and (re)myelination in brain lesions. This is possibly an important cause for incomplete remyelination in the CNS of early stage MS patients and for failure in remyelination when the disease progresses. In this study we address whether under demyelinating conditions in vivo, tissue Transglutaminase (TG2), a Ca(2+) -dependent enzyme that catalyses posttranslational modification of proteins, contributes to extracellular matrix (ECM) deposition and/or aggregation...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28127945/in-vivo-conversion-of-astrocytes-to-myelinating-cells-by-mir-302-367-and-valproate-to-enhance-myelin-repair
#20
Maryam Ghasemi-Kasman, Leila Zare, Hossein Baharvand, Mohammad Javan
Enhancement of repair potential for degenerative brain diseases has been a research priority during recent years. Considering recent advancements in the field of direct transdifferentiation, conversion of astrocytes as a prominent component of glial scars to the progenitor cells that contribute to the repair mechanisms seems interesting. Recently, we have reported miR-302/367-mediated in vivo conversion of astrocytes into neuroblasts and neurons. In the current study, we used miR-302/367 and valproate (VPA) to show the possibility of conversion of astrocytes to oligodendrocyte progenitor cells and myelinating cells in a cuprizone (CPZ)-induced model of demyelination...
January 27, 2017: Journal of Tissue Engineering and Regenerative Medicine
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