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https://www.readbyqxmd.com/read/28629631/probenecid-treatment-reduces-demyelination-induced-by-cuprizone-feeding
#1
Nadine Hainz, Philipp Becker, Daniel Rapp, Stefan Wagenpfeil, Bodo Wonnenberg, Christoph Beisswenger, Thomas Tschernig, Carola Meier
Recent experiments showed that a pannexin-1 inhibitor, probenecid, reduced clinical symptoms in the murine experimental autoimmune encephalomyelitis when applied during the initial phase of neuronal inflammation. An inflammatory component is also present in a toxically induced inflammation and demyelination using cuprizone diet. Probenecid is a pannexin-1 antagonist and a probenecid therapy was investigated. Mice were fed for 10days with a cuprizone diet. In the following, the diet was continued but combined with a daily injection of a low dose of probenecid or solvent for 10days...
June 16, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28599235/a-digital-image-method-of-spot-tests-for-determination-of-copper-in-sugar-cane-spirits
#2
Kenia Dias Pessoa, Willian Toito Suarez, Marina Ferreira Dos Reis, Mathews de Oliveira Krambeck Franco, Renata Pereira Lopes Moreira, Vagner Bezerra Dos Santos
In this work the development and validation of analytical methodology for determination of copper in sugarcane spirit samples is carried out. The digital image based (DIB) method was applied along with spot test from the colorimetric reaction employing the RGB color model. For the determination of copper concentration, it was used the cuprizone - a bidentate organic reagent - which forms with copper a blue chelate in an alkaline medium. A linear calibration curve over the concentration range from 0.75 to 5...
May 31, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28582448/acid-sphingomyelinase-deficiency-enhances-myelin-repair-after-acute-and-chronic-demyelination
#3
Marwan Chami, Ramona Halmer, Laura Schnoeder, Katrin Anne Becker, Carola Meier, Klaus Fassbender, Erich Gulbins, Silke Walter
The cuprizone animal model, also known as the toxic demyelination model, is a well-reproducible model of demyelination- and remyelination in mice, and has been useful in studying important aspect of human demyelinating diseases, including multiple sclerosis. In this study, we investigated the role of acid sphingomyelinase in demyelination and myelin repair by inducing acute and chronic demyelination with 5- or 12-week cuprizone treatment, followed by a 2-week cuprizone withdrawal phase to allow myelin repair...
2017: PloS One
https://www.readbyqxmd.com/read/28576706/rhigm22-enhances-remyelination-in-the-brain-of-the-cuprizone-mouse-model-of-demyelination
#4
Ariana P Mullin, Charlene Cui, Yu Wang, Jing Wang, Erika Troy, Anthony O Caggiano, Tom J Parry, Raymond W Colburn, Elias Pavlopoulos
Failure of oligodendrocyte precursor cells (OPCs) to differentiate and remyelinate axons is thought to be a major cause of the limited ability of the central nervous system to repair plaques of immune-mediated demyelination in multiple sclerosis (MS). Current therapies for MS aim to lessen the immune response in order to reduce the frequency and severity of attacks, but these existing therapies do not target remyelination or stimulate repair of the damaged tissue. Thus, the promotion of OPC differentiation and remyelination is potentially an important therapeutic goal...
May 30, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28575206/heterozygote-galactocerebrosidase-galc-mutants-have-reduced-remyelination-and-impaired-myelin-debris-clearance-following-demyelinating-injury
#5
Nicole J Scott-Hewitt, Christopher J Folts, Jessica M Hogestyn, Gavin Piester, Margot Mayer-Pröschel, Mark D Noble
Genome-wide association studies (GWAS) are identifying multiple genetic risk factors for several diseases, but the functional role of these changes remains mostly unknown. Variants in the galactocerebrosidase (GALC) gene, for example, were identified as a risk factor for Multiple Sclerosis (MS); however, potential biological relevance of GALC variants to MS remains elusive. We found that heterozygote GALC mutant mice have reduced myelin debris clearance and diminished remyelination after a demyelinating insult...
May 31, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28567989/the-novel-synthetic-microneurotrophin-bnn27-protects-mature-oligodendrocytes-against-cuprizone-induced-death-through-the-ngf-receptor-trka
#6
Giulia Bonetto, Ioannis Charalampopoulos, Achille Gravanis, Domna Karagogeos
BNN27, a member of a chemical library of C17-spiroepoxy derivatives of the neurosteroid DHEA, has been shown to regulate neuronal survival through its selective interaction with NGF receptors (TrkA and p75(NTR) ), but its role on glial populations has not been studied. Here, we present evidence that BNN27 provides trophic action (rescue from apoptosis), in a TrkA-dependent manner, to mature oligodendrocytes when they are challenged with the cuprizone toxin in culture. BNN27 treatment also increases oligodendrocyte maturation and diminishes microglia activation in vitro...
August 2017: Glia
https://www.readbyqxmd.com/read/28560740/acutely-damaged-axons-are-remyelinated-in-multiple-sclerosis-and-experimental-models-of-demyelination
#7
Verena Schultz, Franziska van der Meer, Claudia Wrzos, Uta Scheidt, Erik Bahn, Christine Stadelmann, Wolfgang Brück, Andreas Junker
Remyelination is in the center of new therapies for the treatment of multiple sclerosis to resolve and improve disease symptoms and protect axons from further damage. Although remyelination is considered beneficial in the long term, it is not known, whether this is also the case early in lesion formation. Additionally, the precise timing of acute axonal damage and remyelination has not been assessed so far. To shed light onto the interrelation between axons and the myelin sheath during de- and remyelination, we employed cuprizone- and focal lysolecithin-induced demyelination and performed time course experiments assessing the evolution of early and late stage remyelination and axonal damage...
August 2017: Glia
https://www.readbyqxmd.com/read/28556945/leukemia-lymphoma-related-factor-lrf-exhibits-stage-and-context-dependent-transcriptional-controls-in-the-oligodendrocyte-lineage-and-modulates-remyelination
#8
Nathan L Davidson, Fengshan Yu, Naruchorn Kijpaisalratana, Tuan Q Le, Laurel A Beer, Kryslaine L Radomski, Regina C Armstrong
Leukemia/lymphoma-related factor (LRF), a zinc-finger transcription factor encoded by Zbtb7a, is a protooncogene that regulates differentiation in diverse cell lineages, and in the CNS, its function is relatively unexplored. This study is the first to examine the role of LRF in CNS pathology. We first examined LRF expression in a murine viral model of spinal cord demyelination with clinically relevant lesion characteristics. LRF was rarely expressed in oligodendrocyte progenitors (OP) yet, was detected in nuclei of the majority of oligodendrocytes in healthy adult CNS and during remyelination...
May 30, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28549646/increased-central-dopaminergic-activity-might-be-involved-in-the-behavioral-abnormality-of-cuprizone-exposure-mice
#9
Haoxiao Chang, Jianghong Liu, Yifan Zhang, Fang Wang, Yanchuan Wu, Li Zhang, Houxi Ai, Guangliang Chen, Linlin Yin
The neurotoxican cuprizone (CPZ, a copper chelator) has been used extensively to create a mouse model of demyelination. However, the effects on behavior of CPZ treatment have not been reported in C57BL/6 mice given a diet containing 0.4% CPZ within 3weeks. Behavioral abnormalities were assessed using a range of test: Y-maze, spontaneous locomotor activity, rota-rod test, novel object recognition, climbing. Mice exposed to CPZ displayed more arm entrance, locomotor movements, and climbing behavior, suggesting an increase in central nervous system activity...
May 23, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28544286/early-regional-cuprizone-induced-demyelination-in-a-rat-model-revealed-with-mri
#10
Wendy Oakden, Nicholas A Bock, Alia Al-Ebraheem, Michael J Farquharson, Greg J Stanisz
The cuprizone model of demyelination is well established in the mouse as a tool for the study of the mechanisms of both demyelination and remyelination. It is often desirable, however, to have a larger model, such as the rat, especially for imaging-based studies, yet initial work has failed to show demyelination in cuprizone-fed rats. Several recent studies have demonstrated demyelination in the rat, but only in the corpus callosum. In this study, we acquired high-resolution, three-dimensional images of the whole brain every 2 weeks, using a T1 -weighted magnetization-prepared rapid acquisition gradient echo imaging sequence, optimized for myelin contrast, in order to assess myelination across the entire rat brain over a period of 8 weeks on a 1% cuprizone diet...
May 22, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28466255/formyl-peptide-receptor-1-mediated-glial-cell-activation-in-a-mouse-model-of-cuprizone-induced-demyelination
#11
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)...
June 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
#12
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
#13
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
#14
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...
May 27, 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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