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Remyelination

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https://www.readbyqxmd.com/read/28925069/myelin-plasticity-neural-activity-and-traumatic-neural-injury
#1
REVIEW
Bethany R Kondiles, Philip J Horner
The possibility that adult organisms exhibit myelin plasticity has recently become a topic of great interest. Many researchers are exploring the role of myelin growth and adaptation in daily functions such as memory and motor learning. Here we consider evidence for three different potential categories of myelin plasticity: the myelination of previously bare axons, remodeling of existing sheaths, and the removal of a sheath with replacement by a new internode. We also review evidence that points to the importance of neural activity as a mechanism by which oligodendrocyte precursor cells (OPCs) are cued to differentiate into myelinating oligodendrocytes, which may potentially be an important component of myelin plasticity...
September 19, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28925029/loss-of-gas6-and-axl-signaling-results-in-extensive-axonal-damage-motor-deficits-prolonged-neuroinflammation-and-less-remyelination-following-cuprizone-exposure
#2
Alex K Ray, Juwen C DuBois, Ross C Gruber, Hillary M Guzik, Maria E Gulinello, Geoffrey Perumal, Cedric Raine, Lauren Kozakiewicz, Julie Williamson, Bridget Shafit-Zagardo
The TAM (Tyro3, Axl, and MerTK) family of receptor tyrosine kinases (RTKs) and their ligands, Gas6 and ProS1, are important for innate immune responses and central nervous system (CNS) homeostasis. While only Gas6 directly activates Axl, ProS1 activation of Tyro3/MerTK can indirectly activate Axl through receptor heterodimerization. Therefore, we generated Gas6(-/-) Axl(-/-) double knockout (DKO) mice to specifically examine the contribution of this signaling axis while retaining ProS1 signaling through Tyro3 and MerTK...
September 19, 2017: Glia
https://www.readbyqxmd.com/read/28923597/targeting-demyelination-via-%C3%AE-secretases-promoting-sapp%C3%AE-release-to-enhance-remyelination-in-central-nervous-system
#3
Gemma Llufriu-Dabén, Alex Carrete, Elena Chierto, Jo Mailleux, Emeline Camand, Anne Simon, Tim Vanmierlo, Christiane Rose, Bernadette Allinquant, Jerome J A Hendriks, Charbel Massaad, Delphine Meffre, Mehrnaz Jafarian-Tehrani
Remyelination is an endogenous regenerative process of myelin repair in the central nervous system (CNS) with limited efficacy in demyelinating disorders. As strategies enhancing endogenous remyelination become a therapeutic challenge, we have focused our study on α-secretase-induced sAPPα release, a soluble endogenous protein with neuroprotective and neurotrophic properties. However, the role of sAPPα in remyelination is not known. Therefore, we investigated the remyelination potential of α-secretase-induced sAPPα release following CNS demyelination in mice...
September 15, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28923306/the-flavonoid-baicalein-attenuates-cuprizone-induced-demyelination-via-suppression-of-neuroinflammation
#4
Miho Hashimoto, Shinji Yamamoto, Kensuke Iwasa, Kota Yamashina, Masaki Ishikawa, Kei Maruyama, Francesca Bosetti, Keisuke Yoshikawa
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system characterized by recurrent and progressive demyelination/remyelination cycles, neuroinflammation, oligodendrocyte loss, and axonal pathology. Baicalein isolated from the roots of Scutellaria baicalensis has been shown to exert anti-inflammatory and anti-oxidant effects. The cuprizone model is an established mouse model of MS and causes demyelination and motor dysfunction to induce neuroinflammation such as glial activation and pro-inflammatory cytokine production...
September 15, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28905149/interactions-between-the-canonical-wnt-beta-catenin-pathway-and-ppar-gamma-on-neuroinflammation-demyelination-and-remyelination-in-multiple-sclerosis
#5
REVIEW
Alexandre Vallée, Jean-Noël Vallée, Rémy Guillevin, Yves Lecarpentier
Multiple sclerosis (MS) is marked by neuroinflammation and demyelination with loss of oligodendrocytes in the central nervous system. The immune response is regulated by WNT/beta-catenin pathway in MS. Activated NF-kappaB, a major effector of neuroinflammation, and upregulated canonical WNT/beta-catenin pathway positively regulate each other. Demyelinating events present an upregulation of WNT/beta-catenin pathway, whereas proper myelinating phases show a downregulation of WNT/beta-catenin pathway essential for the promotion of oligodendrocytes precursors cells proliferation and differentiation...
September 13, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28904214/after-nerve-injury-lineage-tracing-shows-that-myelin-and-remak-schwann-cells-elongate-extensively-and-branch-to-form-repair-schwann-cells-which-shorten-radically-on-remyelination
#6
Jose A Gomez-Sanchez, Kjara S Pilch, Milou van der Lans, Shaline V Fazal, Cristina Benito, Laura J Wagstaff, Rhona Mirsky, Kristjan R Jessen
There is consensus that, distal to peripheral nerve injury, myelin and Remak cells reorganize to form cellular columns, Bungner's bands, which are indispensable for regeneration. However, knowledge of the structure of these regeneration tracks has not advanced for decades and the structure of the cells that form them, denervated or repair Schwann cells, remains obscure. Furthermore, the origin of these cells from myelin and Remak cells and their ability to give rise to myelin cells after regeneration has not been demonstrated directly, although these conversions are believed to be central to nerve repair...
September 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28899916/gd1a-overcomes-inhibition-of-myelination-by-fibronectin-via-activation-of-protein-kinase-a-implications-for-multiple-sclerosis
#7
Jing Qin, Arend H Sikkema, Kristine van der Bij, Jenny C de Jonge, Karin Klappe, Vera Nies, Johan W Jonker, Jan Willem Kok, Dick Hoekstra, Wia Baron
Remyelination failure by oligodendrocytes contributes to the functional impairment that characterizes the demyelinating disease multiple sclerosis (MS). Since incomplete remyelination will irreversibly damage axonal connections, treatments effectively promoting remyelination are pivotal in halting disease progression. Our previous findings suggest that fibronectin aggregates, as an environmental factor, contribute to remyelination failure by perturbing oligodendrocyte progenitor cell (OPC) maturation. Here, we aim at elucidating whether exogenously added gangliosides, i...
September 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28899915/conditional-deletion-of-the-l-type-calcium-channel-cav1-2-in-ng2-positive-cells-impairs-remyelination-in-mice
#8
Diara A Santiago González, Veronica T Cheli, Norma N Zamora, Tenzing N Lama, Vilma Spreuer, Geoffrey G Murphy, Pablo M Paez
Exploring the molecular mechanisms that drive the maturation of oligodendrocyte progenitor cells (OPCs) during the remyelination process is essential to develop new therapeutic tools to intervene in demyelinating diseases such as Multiple Sclerosis. To determine whether L-type voltage-gated calcium channels (L-VGCCs) are required for OPC development during remyelination, we have generated an inducible conditional knockout mouse in which the L-VGCC isoform Cav1.2 was deleted in NG2 positive OPCs (Cav1.2(KO))...
September 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28885860/anti-lingo-1-opicinumab-a-new-monoclonal-antibody-tested-in-relapsing-remitting-multiple-sclerosis
#9
Serena Ruggieri, Carla Tortorella, Claudio Gasperini
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). The modern treatment era for MS witnessed a growing pool of drugs now available for use in clinical practice. These therapies work at different levels, however there is a lack of treatments acting on the neurodegenerative component or improving mechanism of repair. Areas covered: The latest knowledge about the pathophysiological changes occurring in MS have translated into novel treatments at different stages of development...
September 8, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/28880149/dual-function-of-the-pi3k-akt-mtorc1-axis-in-myelination-of-the-peripheral-nervous-system
#10
Gianluca Figlia, Camilla Norrmén, Jorge A Pereira, Daniel Gerber, Ueli Suter
Myelination is a biosynthetically demanding process in which mTORC1, the gatekeeper of anabolism, occupies a privileged regulatory position. We have shown previously that loss of mTORC1 function in Schwann cells (SCs) hampers myelination. Here, we genetically disrupted key inhibitory components upstream of mTORC1, TSC1 or PTEN, in mouse SC development, adult homeostasis, and nerve injury. Surprisingly, the resulting mTORC1 hyperactivity led to markedly delayed onset of both developmental myelination and remyelination after injury...
September 7, 2017: ELife
https://www.readbyqxmd.com/read/28875931/transient-hypothyroidism-favors-oligodendrocyte-generation-providing-functional-remyelination-in-the-adult-mouse-brain
#11
Sylvie Remaud, Fernando C Ortiz, Marie Perret-Jeanneret, Marie-Stéphane Aigrot, Jean-David Gothié, Csaba Fekete, Zsuzsanna Kvárta-Papp, Balázs Gereben, Dominique Langui, Catherine Lubetzki, Maria Cecilia Angulo, Bernard Zalc, Barbara Demeneix
In the adult brain, both neurons and oligodendrocytes can be generated from neural stem cells located within the Sub-Ventricular Zone (SVZ). Physiological signals regulating neuronal versus glial fate are largely unknown. Here we report that a thyroid hormone (T3)-free window, with or without a demyelinating insult, provides a favorable environment for SVZ-derived oligodendrocyte progenitor generation. After demyelination, oligodendrocytes derived from these newly-formed progenitors provide functional remyelination, restoring normal conduction speed...
September 6, 2017: ELife
https://www.readbyqxmd.com/read/28875862/an-update-on-the-role-of-matrix-metalloproteinases-in-the-pathogenesis-of-multiple-sclerosis
#12
Marina Boziki, Nikolaos Grigoriadis
BACKGROUND: Matrix metalloproteinases (MMPs) are zinc-containing endopeptidases, proteins essential to the degradation of various tissue extracellular matrix proteins. Under normal conditions MMPs participate in several physiological processes, both in the developing organism and the adult. Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS), affecting primarily young adults. Inflammatory infiltrations of the CNS parenchyma by autoreactive immune cells, that mediate myelin degradation in the form of the demyelination "plaque", are the pathological hallmark of the disease...
September 6, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28863829/experimental-models-of-demyelination-and-remyelination
#13
L Torre-Fuentes, L Moreno-Jiménez, V Pytel, J A Matías-Guiu, U Gómez-Pinedo, J Matías-Guiu
INTRODUCTION: Experimental animal models constitute a useful tool to deepen our knowledge of central nervous system disorders. In the case of multiple sclerosis, however, there is no such specific model able to provide an overview of the disease; multiple models covering the different pathophysiological features of the disease are therefore necessary. DEVELOPMENT: We reviewed the different in vitro and in vivo experimental models used in multiple sclerosis research...
August 29, 2017: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/28842413/nf-%C3%AE%C2%BAb-activation-protects-oligodendrocytes-against-inflammation
#14
Sarrabeth Stone, Stephanie Jamison, Yuan Yue, Wilaiwan Durose, Ruth Schmidt-Ullrich, Wensheng Lin
NF-κB is a key player in inflammatory diseases, including multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). However, the effects of NF-κB activation on oligodendrocytes in MS and EAE remain unknown. We generated a mouse model that expresses IκBαΔN, a super-suppressor of NF-κB, specifically in oligodendrocytes and demonstrated that IκBαΔN expression had no effect on oligodendrocytes under normal conditions (both sexes). Interestingly, we showed that oligodendrocyte-specific expression of IκBαΔN blocked NF-κB activation in oligodendrocytes and resulted in exacerbated oligodendrocyte death and hypomyelination in young, developing mice that ectopically express IFN-γ in the CNS (both sexes)...
August 23, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28840755/an-alternative-cuprizone-induced-demyelination-and-remyelination-mouse-model
#15
Wei Zhen, Ailian Liu, Jiaqi Lu, Wandong Zhang, David Tattersall, Jianfei Wang
The cuprizone model is a well-established and investigated paradigm to study demyelination and remyelination in rodents. Cuprizone is usually administrated by mixing in the powdered or pelleted rodent chow. However, since cuprizone is sensitive to the environment and the consumption of it varies between different animals, the major issue is the discrepancy in demyelination of the animals. This study reports the development of the cuprizone model by gavage administrations in mice. Following testing a series of doses of cuprizone, 400 mg/kg/day was found to be the best dosage to induce dramatic and consistent demyelination after 5 weeks of administration; while remyelination quickly occurred after 9 days of cuprizone withdrawal...
July 2017: ASN Neuro
https://www.readbyqxmd.com/read/28834740/pericytes-stimulate-oligodendrocyte-progenitor-cell-differentiation-during-cns-remyelination
#16
Alerie Guzman De La Fuente, Simona Lange, Maria Elena Silva, Ginez A Gonzalez, Herbert Tempfer, Peter van Wijngaarden, Chao Zhao, Ludovica Di Canio, Andrea Trost, Lara Bieler, Pia Zaunmair, Peter Rotheneichner, Anna O'Sullivan, Sebastien Couillard-Despres, Oihana Errea, Maarja A Mäe, Johanna Andrae, Liqun He, Annika Keller, Luis F Bátiz, Christer Betsholtz, Ludwig Aigner, Robin J M Franklin, Francisco J Rivera
The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs) proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs) rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In Pdgfb(ret/ret) mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC) differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in vitro and increased the rate of remyelination in an ex vivo cerebellar slice model of demyelination...
August 22, 2017: Cell Reports
https://www.readbyqxmd.com/read/28825598/peripherally-derived-fgf21-promotes-remyelination-in-the-central-nervous-system
#17
Mariko Kuroda, Rieko Muramatsu, Noriko Maedera, Yoshihisa Koyama, Machika Hamaguchi, Harutoshi Fujimura, Mari Yoshida, Morichika Konishi, Nobuyuki Itoh, Hideki Mochizuki, Toshihide Yamashita
Demyelination in the central nervous system (CNS) leads to severe neurological deficits that can be partially reversed by spontaneous remyelination. Because the CNS is isolated from the peripheral milieu by the blood-brain barrier, remyelination is thought to be controlled by the CNS microenvironment. However, in this work we found that factors derived from peripheral tissue leak into the CNS after injury and promote remyelination in a murine model of toxin-induced demyelination. Mechanistically, leakage of circulating fibroblast growth factor 21 (FGF21), which is predominantly expressed by the pancreas, drives proliferation of oligodendrocyte precursor cells (OPCs) through interactions with β-klotho, an essential coreceptor of FGF21...
August 21, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28822061/co-ultramicronized-palmitoylethanolamide-luteolin-facilitates-the-development-of-differentiating-and-undifferentiated-rat-oligodendrocyte-progenitor-cells
#18
Stephen D Skaper, Massimo Barbierato, Laura Facci, Mila Borri, Gabriella Contarini, Morena Zusso, Pietro Giusti
Oligodendrocytes, the myelin-producing cells of the central nervous system (CNS), have limited capability to bring about repair in chronic CNS neuroinflammatory demyelinating disorders such as multiple sclerosis (MS). MS lesions are characterized by a compromised pool of undifferentiated oligodendrocyte progenitor cells (OPCs) unable to mature into myelin-producing oligodendrocytes. An attractive strategy may be to replace lost OLs and/or promote their maturation. N-palmitoylethanolamine (PEA) is an endogenous fatty acid amide signaling molecule with anti-inflammatory and neuroprotective actions...
August 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28818673/1-25-dihydroxyvitamin-d3-induces-brain-proteomic-changes-in-cuprizone-mice-during-remyelination-involving-calcium-proteins
#19
Eystein Oveland, Agnes Nystad, Frode Berven, Kjell-Morten Myhr, Øivind Torkildsen, Stig Wergeland
Dietary supplementation of vitamin D is commonly recommended to patients with multiple sclerosis. We recently found that high-dose of the hormonally active 1,25-dihydroxyvitamin-D3 (1,25D) promotes myelin repair in the cuprizone model for de- and remyelination. In the present study, we quantified 5062 proteins, of which 125 were differentially regulated in brain tissue from 1,25D treated mice during remyelination, compared to placebo. Proteins upregulated in the early remyelination phase were involved in calcium binding, e...
August 14, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28808113/lncrna-gas5-inhibits-microglial-m2-polarization-and-exacerbates-demyelination
#20
Dingya Sun, Zhongwang Yu, Xue Fang, Mingdong Liu, Yingyan Pu, Qi Shao, Dan Wang, Xiaolin Zhao, Aijun Huang, Zhenghua Xiang, Chao Zhao, Robin Jm Franklin, Li Cao, Cheng He
The regulation of inflammation is pivotal for preventing the development or reoccurrence of multiple sclerosis (MS). A biased ratio of high-M1 versus low-M2 polarized microglia is a major pathological feature of MS Here, using microarray screening, we identify the long noncoding RNA (lncRNA) GAS5 as an epigenetic regulator of microglial polarization. Gain- and loss-of-function studies reveal that GAS5 suppresses microglial M2 polarization. Interference with GAS5 in transplanted microglia attenuates the progression of experimental autoimmune encephalomyelitis (EAE) and promotes remyelination in a lysolecithin-induced demyelination model...
August 14, 2017: EMBO Reports
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