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https://www.readbyqxmd.com/read/28466255/formyl-peptide-receptor-1-mediated-glial-cell-activation-in-a-mouse-model-of-cuprizone-induced-demyelination
#1
Kai Bihler, Eugenia Kress, Stefan Esser, Stella Nyamoya, Simone C Tauber, Tim Clarner, Matthias B Stope, Thomas Pufe, Lars-Ove Brandenburg
Multiple sclerosis (MS) is a chronic degenerative disease of the central nervous system that is characterized by myelin abnormalities, oligodendrocyte pathology, and concomitant glia activation. Unclear are the factors triggering gliosis and demyelination. New findings suggest an important role of the innate immune response in the initiation and progression of active demyelinating lesions. The innate immune response is induced by pathogen-associated or danger-associated molecular patterns, which are identified by pattern recognition receptors (PRRs), including the G-protein coupled with formyl peptide receptors (FPRs)...
May 2, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28447514/neuroprotective-effects-of-ellagic-acid-on-cuprizone-induced-acute-demyelination-through-limitation-of-microgliosis-adjustment-of-cxcl12-il-17-il-11-axis-and-restriction-of-mature-oligodendrocytes-apoptosis
#2
Nima Sanadgol, Fereshteh Golab, Zakiyeh Tashakkor, Nooshin Taki, Samira Moradi Kouchi, Ali Mostafaie, Mehdi Mehdizadeh, Mohammad Abdollahi, Ghorban Taghizadeh, Mohammad Sharifzadeh
CONTEXT: Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuropathologic conditions. OBJECTIVE: In vivo neuroprotective effects of EA on cuprizone (cup)-induced demyelination were evaluated. MATERIAL AND METHODS: C57BL/6 J mice were fed with chow containing 0.2% cup for 4 weeks to induce oligodendrocytes (OLGs) depletion predominantly in the corpus callosum (CC)...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28436460/histological-validation-of-fast-macromolecular-proton-fraction-mapping-as-a-quantitative-myelin-imaging-method-in-the-cuprizone-demyelination-model
#3
Marina Yu Khodanovich, Irina V Sorokina, Valentina Yu Glazacheva, Andrey E Akulov, Nikolay M Nemirovich-Danchenko, Alexander V Romashchenko, Tatyana G Tolstikova, Lilia R Mustafina, Vasily L Yarnykh
Cuprizone-induced demyelination in mice is a frequently used model in preclinical multiple sclerosis research. A recent quantitative clinically-targeted MRI method, fast macromolecular proton fraction (MPF) mapping demonstrated a promise as a myelin biomarker in human and animal studies with a particular advantage of sensitivity to both white matter (WM) and gray matter (GM) demyelination. This study aimed to histologically validate the capability of MPF mapping to quantify myelin loss in brain tissues using the cuprizone demyelination model...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28427937/reactivity-of-anti-hnk-1-antibodies-to-branched-o-mannose-glycans-associated-with-demyelination
#4
Kanoko Sakuda, Yasuhiko Kizuka, Yoshiki Yamaguchi, Katsunori Tanaka, Ken Ogiwara, Tatsuya Segawa, Yoshiaki Hagiwara, Ichiro Matsuo, Haruko Ogawa, Naoyuki Taniguchi, Shinobu Kitazume
Human natural killer-1 (HNK-1) epitope, a highly-expressed glycan in the nervous system, is critical for normal synaptic plasticity and spatial learning. HNK-1 epitope modifies N-glycans on several neural glycoproteins, and also modifies O-mannosyl glycans. A branching enzyme for O-mannosyl glycans (GnT-IX, Core M2 synthase) exhibits brain-specific expression, and the product core M2 glycans are also limited to the brain. In a previous study, we showed that cuprizone-induced demyelination increased HNK-1-capped core M2 glycan expression, while GnT-IX deficiency ameliorated demyelination, suggesting that these glycans could be useful diagnostic markers for demyelination status and act as therapeutic targets...
April 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28422748/therapeutic-inhibition-of-soluble-brain-tnf-promotes-remyelination-by-increasing-myelin-phagocytosis-by-microglia
#5
Maria Karamita, Christopher Barnum, Wiebke Möbius, Malú G Tansey, David E Szymkowski, Hans Lassmann, Lesley Probert
Multiple sclerosis (MS) is an inflammatory CNS demyelinating disease in which remyelination largely fails. Transmembrane TNF (tmTNF) and TNF receptor 2 are important for remyelination in experimental MS models, but it is unknown whether soluble TNF (solTNF), a major proinflammatory factor, is involved in regeneration processes. Here, we investigated the specific contribution of solTNF to demyelination and remyelination in the cuprizone model. Treatment with XPro1595, a selective inhibitor of solTNF that crosses the intact blood-brain barrier (BBB), in cuprizone-fed mice did not prevent toxin-induced oligodendrocyte loss and demyelination, but it permitted profound early remyelination due to improved phagocytosis of myelin debris by CNS macrophages and prevented disease-associated decline in motor performance...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28404595/nlr-members-nlrc4-and-nlrp3-mediate-sterile-inflammasome-activation-in-microglia-and-astrocytes
#6
Leslie Freeman, Haitao Guo, Clément N David, W June Brickey, Sushmita Jha, Jenny P-Y Ting
Inflammation in the brain accompanies several high-impact neurological diseases including multiple sclerosis (MS), stroke, and Alzheimer's disease. Neuroinflammation is sterile, as damage-associated molecular patterns rather than microbial pathogens elicit the response. The inflammasome, which leads to caspase-1 activation, is implicated in neuroinflammation. In this study, we reveal that lysophosphatidylcholine (LPC), a molecule associated with neurodegeneration and demyelination, elicits NLRP3 and NLRC4 inflammasome activation in microglia and astrocytes, which are central players in neuroinflammation...
May 1, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28394030/the-effect-of-realistic-geometries-on-the-susceptibility-weighted-mr-signal-in-white-matter
#7
Tianyou Xu, Sean Foxley, Michiel Kleinnijenhuis, Way Cherng Chen, Karla L Miller
PURPOSE: To investigate the effect of realistic microstructural geometry on the susceptibility-weighted MR signal in white matter (WM), with application to demyelination. METHODS: Previous work has modeled susceptibility-weighted signals under the assumption that axons are cylindrical. In this study, we explored the implications of this assumption by considering the effect of more realistic geometries. A three-compartment WM model incorporating relevant properties based on the literature was used to predict the MR signal...
April 10, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28341402/inhibitors-of-protein-arginine-deiminases-and-their-efficacy-in-animal-models-of-multiple-sclerosis
#8
Amit Sarswat, Ewa Wasilewski, Sai K Chakka, Angelica M Bello, Andrew V Caprariello, Chithra M Muthuramu, Peter K Stys, Shannon E Dunn, Lakshmi P Kotra
Protein arginine deiminases (PAD) are implicated in a variety of inflammatory and neurodegenerative diseases including multiple sclerosis (MS). Following the discovery of an in silico hit containing hydantoin and a piperidine moiety, we hypothesized that a 2-carbon linker on the hydantoin would be necessary for a 5-membered heterocycle for optimal PAD inhibitory activity. We designed thirteen compounds as potential inhibitors of PAD2 and PAD4 enzymes-two important PAD enzymes implicated in MS. Two compounds, one with an imidazole moiety (22) and the other with a tetrazole moiety (24) showed good inhibition of PAD isozymes in vitro and in the EAE mouse model of MS in vivo...
March 6, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28289377/loss-of-saltation-and-presynaptic-action-potential-failure-in-demyelinated-axons
#9
Mustafa S Hamada, Marko A Popovic, Maarten H P Kole
In cortical pyramidal neurons the presynaptic terminals controlling transmitter release are located along unmyelinated axon collaterals, far from the original action potential (AP) initiation site, the axon initial segment (AIS). Once initiated, APs will need to reliably propagate over long distances and regions of geometrical inhomogeneity like branch points (BPs) to rapidly depolarize the presynaptic terminals and confer temporally precise synaptic transmission. While axon pathologies such as demyelinating diseases are well established to impede the fidelity of AP propagation along internodes, to which extent myelin loss affects propagation along BPs and axon collaterals is not well understood...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28238799/inhibition-of-drp1-hyper-activation-is-protective-in-animal-models-of-experimental-multiple-sclerosis
#10
Fucheng Luo, Karl Herrup, Xin Qi, Yan Yang
Multiple Sclerosis (MS), a leading neurological disorder of young adults, is characterized by the loss of oligodendrocytes (OLs), demyelination, inflammation and neuronal degeneration. Here we show that dynamin-related protein 1 (Drp1), a mitochondrial fission protein, is activated in primary OL cells exposed to TNF-α induced inflammation or oxidative stress, as well as in EAE-immunized and cuprizone toxicity-induced demyelinating mouse models. Inhibition of Drp1 hyper-activation by the selective inhibitor P110 abolishes Drp1 translocation to the mitochondria, reduces mitochondrial fragmentation and stems necrosis in primary OLs exposed to TNF-α and H2O2...
February 24, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28238065/cuprizone-containing-pellets-are-less-potent-to-induce-consistent-demyelination-in-the-corpus-callosum-of-c57bl-6-mice
#11
Tanja Hochstrasser, Gianna Lisa Exner, Stella Nyamoya, Christoph Schmitz, Markus Kipp
The chopper chelator cuprizone serves as a valuable chemical tool to induce consistent and reproducible demyelination in the central nervous system. However, the daily preparation of fresh cuprizone powder mixed in finely ground rodent chow might well be a particular health problem. Alternative methods, such as the fabrication of cuprizone-containing pellets, are available. The effectiveness of this method is, however, not known. In the present study, we compared whether intoxication of C57BL/6 mice with 0...
February 25, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28237816/mir-146a-promotes-remyelination-in-a-cuprizone-model-of-demyelinating-injury
#12
Jing Zhang, Zheng Gang Zhang, Mei Lu, Xinli Wang, Xia Shang, Stanton B Elias, Michael Chopp
The death of mature oligodendrocytes (OLs) which are the sole myelinating cells of the central nervous system (CNS), leads to demyelination and functional deficits. Currently, there is lack of effective remyelination therapies for patients with demyelinating diseases. MicroRNAs (miRNAs) mediate OL function. We hypothesized that miR-146a, by inactivating interleukin-1 receptor-associated kinase 1 (IRAK1), promotes differentiation of oligodendrocyte progenitor cells (OPCs) and thereby enhances remyelination. To test this hypothesis, a demyelination model induced by a cuprizone (CPZ) diet was employed, in which C57BL/6J mice were fed with a CPZ diet for 5weeks...
February 23, 2017: Neuroscience
https://www.readbyqxmd.com/read/28196893/phosphorylation-of-%C3%AE-b-crystallin-supports-reactive-astrogliosis-in-demyelination
#13
Hedwich F Kuipers, Jane Yoon, Jack van Horssen, May H Han, Paul L Bollyky, Theo D Palmer, Lawrence Steinman
The small heat shock protein αB-crystallin (CRYAB) has been implicated in multiple sclerosis (MS) pathogenesis. Earlier studies have indicated that CRYAB inhibits inflammation and attenuates clinical disease when administered in the experimental autoimmune encephalomyelitis model of MS. In this study, we evaluated the role of CRYAB in primary demyelinating events. Using the cuprizone model of demyelination, a noninflammatory model that allows the analysis of glial responses in MS, we show that endogenous CRYAB expression is associated with increased severity of demyelination...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28186720/cuprizone-intoxication-induces-cell-intrinsic-alterations-in-oligodendrocyte-metabolism-independent-of-copper-chelation
#14
Alexandra Taraboletti, Tia Walker, Robin Avila, He Huang, Joel Caporoso, Erendra Manandhar, Thomas C Leeper, David A Modarelli, Satish Medicetty, Leah P Shriver
Cuprizone intoxication is a common animal model used to test myelin regenerative therapies for the treatment of diseases such as multiple sclerosis. Mice fed this copper chelator develop reversible, region-specific oligodendrocyte loss and demyelination. While the cellular changes influencing the demyelinating process have been explored in this model, there is no consensus about the biochemical mechanisms of toxicity in oligodendrocytes and about whether this damage arises from the chelation of copper in vivo...
March 14, 2017: Biochemistry
https://www.readbyqxmd.com/read/28161197/icariin-enhances-remyelination-process-after-acute-demyelination-induced-by-cuprizone-exposure
#15
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/28153692/chronic-demyelination-induced-seizures
#16
Andrew S Lapato, Jenny I Szu, Jonathan P C Hasselmann, Anna J Khalaj, Devin K Binder, Seema K Tiwari-Woodruff
Multiple sclerosis (MS) patients are three to six times more likely to develop epilepsy compared to the rest of the population. Seizures are more common in patients with early onset or progressive forms of the disease and prognosticate rapid progression to disability and death. Gray matter atrophy, hippocampal lesions, interneuron loss, and elevated juxtacortical lesion burden have been identified in MS patients with seizures; however, translational studies aimed at elucidating the pathophysiological processes underlying MS epileptogenesis are limited...
March 27, 2017: Neuroscience
https://www.readbyqxmd.com/read/28145507/transplanted-mir-219-overexpressing-oligodendrocyte-precursor-cells-promoted-remyelination-and-improved-functional-recovery-in-a-chronic-demyelinated-model
#17
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/28128219/astrocyte-derived-tissue-transglutaminase-affects-fibronectin-deposition-but-not-aggregation-during-cuprizone-induced-demyelination
#18
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
#19
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
https://www.readbyqxmd.com/read/28124770/the-effect-of-stereotactic-injections-on-demyelination-and-remyelination-a-study-in-the-cuprizone-model
#20
Laura Salinas Tejedor, Tanja Wostradowski, Stefan Gingele, Thomas Skripuletz, Viktoria Gudi, Martin Stangel
Remyelination is the natural repair mechanism in demyelinating disorders of the central nervous system (CNS) such as multiple sclerosis. Several animal models have been used to study demyelination and remyelination. Among toxic animal models, oral administration of the toxin cuprizone leads to white and gray matter demyelination. In contrast, focal demyelination models include the stereotactic application of a toxin such as lysolecithin or ethidium bromide. The injection procedure generates a local disruption of the blood-brain barrier (BBB) and might thus trigger a local inflammatory reaction and consequently may influence demyelination and remyelination...
April 2017: Journal of Molecular Neuroscience: MN
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