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https://www.readbyqxmd.com/read/28346104/bioengineered-3d-glial-cell-culture-systems-and-applications-for-neurodegeneration-and-neuroinflammation
#1
P Marc D Watson, Edel Kavanagh, Gary Allenby, Matthew Vassey
Neurodegeneration and neuroinflammation are key features in a range of chronic central nervous system (CNS) diseases such as Alzheimer's and Parkinson's disease, as well as acute conditions like stroke and traumatic brain injury, for which there remains significant unmet clinical need. It is now well recognized that current cell culture methodologies are limited in their ability to recapitulate the cellular environment that is present in vivo, and there is a growing body of evidence to show that three-dimensional (3D) culture systems represent a more physiologically accurate model than traditional two-dimensional (2D) cultures...
February 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28345117/inwardly-rectifying-k-currents-in-cultured-oligodendrocytes-from-rat-optic-nerve-are-insensitive-to-ph
#2
Alberto Pérez-Samartín, Edith Garay, Juan Pablo H Moctezuma, Abraham Cisneros-Mejorado, María Victoria Sánchez-Gómez, Guadalupe Martel-Gallegos, Leticia Robles-Martínez, Manuel Canedo-Antelo, Carlos Matute, Rogelio O Arellano
Inwardly rectifying K(+) (Kir) channel expression signals at an advanced stage of maturation during oligodendroglial differentiation. Knocking down their expression halts the generation of myelin and produces severe abnormalities in the central nervous system. Kir4.1 is the main subunit involved in the tetrameric structure of Kir channels in glial cells; however, the precise composition of Kir channels expressed in oligodendrocytes (OLs) remains partially unknown, as participation of other subunits has been proposed...
March 27, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28344151/enhancing-oligodendrocyte-differentiation-by-transient-transcription-activation-via-dna-nanoparticle-mediated-transfection
#3
Xiaowei Li, Stephany Y Tzeng, Camila Gadens Zamboni, Vassilis E Koliatsos, Guo-Li Ming, Jordan J Green, Hai-Quan Mao
Current approaches to derive oligodendrocytes from human pluripotent stem cells (hPSCs) need extended exposure of hPSCs to growth factors and small molecules, which limits their clinical application because of the lengthy culture time required and low generation efficiency of myelinating oligodendrocytes. Compared to extrinsic growth factors and molecules, oligodendrocyte differentiation and maturation can be more effectively modulated by regulation of the cell transcription network. In the developing central nervous system (CNS), two basic helix-loop-helix transcription factors, Olig1 and Olig2, are decisive in oligodendrocyte differentiation and maturation...
March 23, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28344001/inducible-and-deterministic-forward-programming-of-human-pluripotent-stem-cells-into-neurons-skeletal-myocytes-and-oligodendrocytes
#4
Matthias Pawlowski, Daniel Ortmann, Alessandro Bertero, Joana M Tavares, Roger A Pedersen, Ludovic Vallier, Mark R N Kotter
The isolation or in vitro derivation of many human cell types remains challenging and inefficient. Direct conversion of human pluripotent stem cells (hPSCs) by forced expression of transcription factors provides a potential alternative. However, deficient inducible gene expression in hPSCs has compromised efficiencies of forward programming approaches. We have systematically optimized inducible gene expression in hPSCs using a dual genomic safe harbor gene-targeting strategy. This approach provides a powerful platform for the generation of human cell types by forward programming...
March 13, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28340598/myelin-specific-multiple-sclerosis-antibodies-cause-complement-dependent-oligodendrocyte-loss-and-demyelination
#5
Yiting Liu, Katherine S Given, Danielle E Harlow, Adeline M Matschulat, Wendy B Macklin, Jeffrey L Bennett, Gregory P Owens
Intrathecal immunoglobulin G (IgG) synthesis, cerebrospinal fluid (CSF) oligoclonal IgG bands and lesional IgG deposition are seminal features of multiple sclerosis (MS) disease pathology. Both the specific targets and pathogenic effects of MS antibodies remain poorly characterized. We produced IgG1 monoclonal recombinant antibodies (rAbs) from clonally-expanded plasmablasts recovered from MS patient CSF. Among these were a subset of myelin-specific MS rAbs. We examined their immunoreactivity to mouse organotypic cerebellar slices by live binding and evaluated tissue injury in the presence and absence of human complement...
March 24, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28336932/tmeff2-is-expressed-in-differentiating-oligodendrocytes-but-dispensable-for-their-differentiation-in-vivo
#6
Hao Huang, Peng Teng, Ruyi Mei, Aifen Yang, Zunyi Zhang, Xiaofeng Zhao, Mengsheng Qiu
Myelin elaborated by oligodendrocytes (OLs) in the central nervous system (CNS) is required for saltatory conduction of action potentials along neuronal axons. We found that TMEFF2, a transmembrane protein with EGF-like and two follistatin-like domains, is selectively expressed in differentiating/myelinating OLs. Previous studies showed that TMEFF2 is capable of binding to PDGFA, which plays important roles in the proliferation, migration and differentiation of oligodendrocyte progenitor cells (OPCs). However, molecular and genetic analysis revealed that Tmeff2 is a weak binder of PDGFA, and not required for OL differentiation and myelin gene expression in vivo...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28334990/insulin-resistance-and-exendin-4-treatment-for-multiple-system-atrophy
#7
Fares Bassil, Marie-Hélène Canron, Anne Vital, Erwan Bezard, Yazhou Li, Nigel H Greig, Seema Gulyani, Dimitrios Kapogiannis, Pierre-Olivier Fernagut, Wassilios G Meissner
Multiple system atrophy is a fatal sporadic adult-onset neurodegenerative disorder with no symptomatic or disease-modifying treatment available. The cytopathological hallmark of multiple system atrophy is the accumulation of α-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Impaired insulin/insulin-like growth factor-1 signalling (IGF-1) and insulin resistance (i.e. decreased insulin/IGF-1) have been reported in other neurodegenerative disorders such as Alzheimer's disease. Increasing evidence also suggests impaired insulin/IGF-1 signalling in multiple system atrophy, as corroborated by increased insulin and IGF-1 plasma concentrations in multiple system atrophy patients and reduced IGF-1 brain levels in a transgenic mouse model of multiple system atrophy...
March 14, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334918/adaptive-human-immunity-drives-remyelination-in-a-mouse-model-of-demyelination
#8
Mohamed El Behi, Charles Sanson, Corinne Bachelin, Léna Guillot-Noël, Jennifer Fransson, Bruno Stankoff, Elisabeth Maillart, Nadège Sarrazin, Vincent Guillemot, Hervé Abdi, Isabelle Cournu-Rebeix, Bertrand Fontaine, Violetta Zujovic
One major challenge in multiple sclerosis is to understand the cellular and molecular mechanisms leading to disease severity progression. The recently demonstrated correlation between disease severity and remyelination emphasizes the importance of identifying factors leading to a favourable outcome. Why remyelination fails or succeeds in multiple sclerosis patients remains largely unknown, mainly because remyelination has never been studied within a humanized pathological context that would recapitulate major events in plaque formation such as infiltration of inflammatory cells...
February 22, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28332093/pathogenic-implications-of-distinct-patterns-of-iron-and-zinc-in-chronic-ms-lesions
#9
Bogdan F Popescu, Josa M Frischer, Samuel M Webb, Mylyne Tham, Reginald C Adiele, Christopher A Robinson, Patrick D Fitz-Gibbon, Stephen D Weigand, Imke Metz, Susan Nehzati, Graham N George, Ingrid J Pickering, Wolfgang Brück, Simon Hametner, Hans Lassmann, Joseph E Parisi, Guo Yong, Claudia F Lucchinetti
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) in which oligodendrocytes, the CNS cells that stain most robustly for iron and myelin are the targets of injury. Metals are essential for normal CNS functioning, and metal imbalances have been linked to demyelination and neurodegeneration. Using a multidisciplinary approach involving synchrotron techniques, iron histochemistry and immunohistochemistry, we compared the distribution and quantification of iron and zinc in MS lesions to the surrounding normal appearing and periplaque white matter, and assessed the involvement of these metals in MS lesion pathogenesis...
March 22, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28327523/methodological-challenges-in-protein-microarray-and-immunohistochemistry-for-the-discovery-of-novel-autoantibodies-in-paediatric-acute-disseminated-encephalomyelitis
#10
Patrick Peschl, Melanie Ramberger, Romana Höftberger, Karin Jöhrer, Matthias Baumann, Kevin Rostásy, Markus Reindl
Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune-mediated demyelinating disease affecting mainly children and young adults. Differentiation to multiple sclerosis is not always possible, due to overlapping clinical symptoms and recurrent and multiphasic forms. Until now, immunoglobulins reactive to myelin oligodendrocyte glycoprotein (MOG antibodies) have been found in a subset of patients with ADEM. However, there are still patients lacking autoantibodies, necessitating the identification of new autoantibodies as biomarkers in those patients...
March 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28326889/aquaporin-4-autoimmunity-in-patients-with-systemic-lupus-erythematosus-a-predominantly-population-based-study
#11
Nasrin Asgari, Sven Jarius, Helle Laustrup, Hanne Pb Skejoe, Soeren T Lillevang, Brian G Weinshenker, Anne Voss
BACKGROUND: Serum immunoglobulin G targeting the astrocyte water channel aquaporin-4 (AQP4) in the central nervous system (CNS) is a biomarker for neuromyelitis optica spectrum disease (NMOSD). Co-existence of NMOSD with systemic lupus erythematosus (SLE) putatively suggests susceptibility to antibody-mediated autoimmune disease. OBJECTIVE: To estimate the prevalence of NMOSD in SLE and investigate the immunogenetic background for an association of NMOSD and SLE...
March 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28326060/microbial-neuraminidase-induces-a-moderate-and-transient-myelin-vacuolation-independent-of-complement-system-activation
#12
Pablo Granados-Durán, María Dolores López-Ávalos, Manuel Cifuentes, Margarita Pérez-Martín, María Del Mar Fernández-Arjona, Timothy R Hughes, Krista Johnson, B Paul Morgan, Pedro Fernández-Llebrez, Jesús M Grondona
AIMS: Some central nervous system pathogens express neuraminidase (NA) on their surfaces. In the rat brain, a single intracerebroventricular (ICV) injection of NA induces myelin vacuolation in axonal tracts. Here, we explore the nature, the time course, and the role of the complement system in this damage. METHODS: The spatiotemporal analysis of myelin vacuolation was performed by optical and electron microscopy. Myelin basic protein-positive area and oligodendrocyte transcription factor (Olig2)-positive cells were quantified in the damaged bundles...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28322741/evidence-of-k-homeostasis-disruption-in-cellular-dysfunction-triggered-by-7-ketocholesterol-24s-hydroxycholesterol-and-tetracosanoic-acid-c24-0-in-158n-murine-oligodendrocytes
#13
Maryem Bezine, Meryam Debbabi, Thomas Nury, Rym Ben-Khalifa, Mohammad Samadi, Mustapha Cherkaoui-Malki, Anne Vejux, Jérôme de Sèze, Thibault Moreau, Mohamed El-Ayeb, Gérard Lizard
Imbalance in the homeostasis of K(+) ions has been reported to contribute to the pathogenesis of neurodegenerative diseases. 7-ketocholesterol (7KC), 24S-hydroxycholesterol (24S-OHC), and tetracosanoic acid (C24:0), often found at increased levels in patients with Alzheimer's disease, Multiple Sclerosis and X-ALD, are able to trigger numerous nerve cell dysfunctions. We therefore studied the impact of 7KC, 24S-OHC, and C24:0 on 158N murine oligodendrocytes, and determined their impact on K(+) homeostasis. The effects of 7KC, 24S-OHC and C24:0 on lipid membrane organization and membrane potential were examined with merocyanine 540 (MC540) and bis-(1,3-diethylthiobarbituric acid) trimethine oxonol (DiSBAC2(3)), respectively...
March 17, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28322157/diabetes-related-neurological-implications-and-pharmacogenomics
#14
Rojas Carranza Camilo Andrés, Bustos Cruz Rosa Helena, Pino Pinzón Carmen Juliana, Ariza Marquez Yeimy Viviana, Gómez Bello Rosa Margarita, Cañadas Garre Marisa
Diabetes mellitus (DM) is the most commonly occurring cause of neuropathy around the world and is beginning to grow in countries where there is a risk of obesity. DM Type II, (T2DM) is a common age-related disease and is a major health concern, particularly in developed countries in Europe where the population is aging. T2DM is a chronic disease which is characterised by hyperglycemia, hyperinsulinemia and insulin resistance, together with the body's inability to use glucose as energy. Such metabolic disorder produces a chronic inflammatory state, as well as changes in lipid metabolism leading to hypertriglyceridemia, thereby producing chronic deterioration of the organs and premature morbidity and mortality...
March 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28321419/pvaxhsp65-vaccination-primes-for-high-il-10-production-and-decreases-experimental-encephalomyelitis-severity
#15
Sofia Fernanda Gonçalves Zorzella-Pezavento, Fernanda Chiuso-Minicucci, Thais Graziela Donegá França, Larissa Lumi Watanabe Ishikawa, Larissa Camargo da Rosa, Priscila Maria Colavite, Bianca Balbino, Camila Marques, Maura Rosane Valerio Ikoma, Ana Paula Masson, Célio Lopes Silva, Alexandrina Sartori
Experimental autoimmune encephalomyelitis (EAE) is a demyelinating pathology of the central nervous system (CNS) used as a model to study multiple sclerosis immunopathology. EAE has also been extensively employed to evaluate potentially therapeutic schemes. Considering the presence of an immune response directed to heat shock proteins (hsps) in autoimmune diseases and the immunoregulatory potential of these molecules, we evaluated the effect of a previous immunization with a genetic vaccine containing the mycobacterial hsp65 gene on EAE development...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28317842/bde-99-impairs-differentiation-of-human-and-mouse-npcs-into-the-oligodendroglial-lineage-by-species-specific-modes-of-action
#16
Katharina Dach, Farina Bendt, Ulrike Huebenthal, Susanne Giersiefer, Pamela J Lein, Heike Heuer, Ellen Fritsche
Polybrominated diphenyl ethers (PBDEs) are bioaccumulating flame retardants causing developmental neurotoxicity (DNT) in humans and rodents. Their DNT effects are suspected to involve thyroid hormone (TH) signaling disruption. Here, we tested the hypothesis whether disturbance of neural progenitor cell (NPC) differentiation into the oligodendrocyte lineage (O4(+) cells) by BDE-99 involves disruption of TH action in human and mouse (h,m)NPCs. Therefore, we quantified differentiation of NPCs into O4(+) cells and measured their maturation via expression of myelin-associated genes (hMBP, mMog) in presence and absence of TH and/or BDE-99...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317272/roles-of-ng2-glia-in-ischemic-stroke
#17
REVIEW
Fei-Er Song, Jia-Lv Huang, Si-Han Lin, Shuo Wang, Guo-Fen Ma, Xiao-Ping Tong
Recent studies have shown that a widely distributed class of glial cells, termed NG2-glia, engages in rapid signaling with surrounding neurons through direct synaptic contacts in the developing and mature central nervous system (CNS). This unique glial cell group has a typical function of proliferating and differentiating into oligodendrocytes during early development of the brain, which is crucial to axon myelin formation. Therefore, NG2-glia are also called oligodendrocyte precursor cells (OPCs). In vitro and in vivo studies reveal that NG2-glia expressing receptors and ion channels demonstrate functional significance for rapid signaling with neuronal synapses and modulation of neuronal activities in both physiological and pathological conditions...
March 19, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28317180/anti-acsa-2-defines-a-novel-monoclonal-antibody-for-prospective-isolation-of-living-neonatal-and-adult-astrocytes
#18
Christina G Kantzer, Camille Boutin, Ina D Herzig, Carolina Wittwer, Sandy Reiß, Marie Catherine Tiveron, Jan Drewes, Thomas D Rockel, Stefanie Ohlig, Jovica Ninkovic, Harold Cremer, Sandra Pennartz, Melanie Jungblut, Andreas Bosio
Astrocytes are the most abundant cell type of the central nervous system and cover a broad range of functionalities. We report here the generation of a novel monoclonal antibody, anti-astrocyte cell surface antigen-2 (Anti-ACSA-2). Flow cytometry, immunohistochemistry and immunocytochemistry revealed that Anti-ACSA-2 reacted specifically with a not yet identified glycosylated surface molecule of murine astrocytes at all developmental stages. It did not show any labeling of non-astroglial cells such as neurons, oligodendrocytes, NG2(+) cells, microglia, endothelial cells, leukocytes, or erythrocytes...
March 20, 2017: Glia
https://www.readbyqxmd.com/read/28306572/neuromyelitis-optica-and-neuromyelitis-optica-spectrum-disorders
#19
Romain Marignier, Alvaro Cobo Calvo, Sandra Vukusic
PURPOSE OF REVIEW: The discovery of highly specific auto-antibodies directed against the water channel aquaporin 4 was a quantum leap in the definition, classification and management of neuromyelitis optica (NMO). Herein, we propose an update on epidemiological, clinical and therapeutic advances in the field, underlining unmet needs. RECENT FINDINGS: Large-scale epidemiological studies have recently provided a more precise evaluation of NMO prevalence and a better stratification regarding ethnicity and sex...
March 16, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28306359/spinal-cord-injuries-how-could-cell-therapy-help
#20
Anna Badner, Ahad M Siddiqui, Michael G Fehlings
Spinal cord injury (SCI) is a devastating condition, where regenerative failure and cell loss lead to paralysis. The heterogeneous and time-sensitive pathophysiology has made it difficult to target tissue repair. Despite many medical advances, there are no effective regenerative therapies. As stem cells offer multi-targeted and environmentally responsive benefits, cell therapy is a promising treatment approach. Areas covered: This review highlights the cell therapies being investigated for SCI, including Schwann cells, olfactory ensheathing cells, mensenchymal stem/stromal cells, neural precursors, oligodendrocyte progenitors, embryonic stem cells, and induced pluripotent stem cells...
March 27, 2017: Expert Opinion on Biological Therapy
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