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https://www.readbyqxmd.com/read/28238799/inhibition-of-drp1-hyper-activation-is-protective-in-animal-models-of-experimental-multiple-sclerosis
#1
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 23, 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
#2
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
#3
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 5 weeks...
February 22, 2017: Neuroscience
https://www.readbyqxmd.com/read/28196893/phosphorylation-of-%C3%AE-b-crystallin-supports-reactive-astrogliosis-in-demyelination
#4
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 14, 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
#5
Alexandra Taraboletti, Tia Louise 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 to treat 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 on the biochemical mechanisms of toxicity in oligodendrocytes and if this damage arises from the chelation of copper in vivo. Here we have identified an oligodendroglial cell line that displays sensitivity to cuprizone toxicity and performed global metabolomic profiling to determine biochemical pathways altered by this treatment...
February 10, 2017: Biochemistry
https://www.readbyqxmd.com/read/28161197/icariin-enhances-remyelination-process-after-acute-demyelination-induced-by-cuprizone-exposure
#6
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
#7
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...
January 30, 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
#8
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
#9
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
#10
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
#11
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...
January 26, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28124768/investigation-of-cuprizone-inactivation-by-temperature
#12
Sandra Heckers, Nadine Held, Jessica Kronenberg, Thomas Skripuletz, Andre Bleich, Viktoria Gudi, Martin Stangel
Animal models, such as cuprizone (bis-cyclohexanone oxaldihydrazone) feeding, are helpful to study experimental demyelination and remyelination in the context of diseases like multiple sclerosis. Cuprizone is a copper chelator, which when supplemented to the normal food of C57BL/6J mice in a concentration of 0.2% leads to oligodendroglial loss, subsequent microglia and astrocyte activation, resulting in demyelination. Termination of the cuprizone diet results in remyelination, promoted by newly formed mature oligodendrocytes...
January 26, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28117328/dietary-cholesterol-promotes-repair-of-demyelinated-lesions-in-the-adult-brain
#13
Stefan A Berghoff, Nina Gerndt, Jan Winchenbach, Sina K Stumpf, Leon Hosang, Francesca Odoardi, Torben Ruhwedel, Carolin Böhler, Benoit Barrette, Ruth Stassart, David Liebetanz, Payam Dibaj, Wiebke Möbius, Julia M Edgar, Gesine Saher
Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is unclear. Here, we show the relationship between cholesterol, myelination and neurological parameters in mouse models of demyelination and remyelination. In the cuprizone model, acute disease reduces serum cholesterol levels that can be restored by dietary cholesterol...
January 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28114887/the-effect-of-omega-3-fatty-acids-on-central-nervous-system-remyelination-in-fat-1-mice
#14
Elise Siegert, Friedemann Paul, Michael Rothe, Karsten H Weylandt
BACKGROUND: There is a large body of experimental evidence suggesting that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are capable of modulating immune function. Some studies have shown that these PUFAs might have a beneficial effect in patients suffering form multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system (CNS). This could be due to increased n-3 PUFA-derived anti-inflammatory lipid mediators. In the present study we tested the effect of an endogenously increased n-3 PUFA status on cuprizone-induced CNS demyelination and remyelination in fat-1 mice versus their wild-type (wt) littermates...
January 24, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/27935632/ultrastructural-abnormalities-and-loss-of-myelinated-fibers-in-the-corpus-callosum-of-demyelinated-mice-induced-by-cuprizone
#15
Yun Xiu, Guo-Hua Cheng, Chao Peng, Yun Wang, Yong-de Li, Feng-Lei Chao, Yong Tang
It is now accepted that white matter abnormalities play an important role in demyelinating diseases and a wide range of psychiatric disorders. Experimental demyelination (especially induced by cuprizone) has been investigated extensively. However, details regarding demyelination and ultrastructural changes of myelinated fibers have not been previously reported. Therefore, we determined the extent of demyelination using quantitative stereology. Mice exposed to cuprizone in the current study showed abnormal anxiety-like behavior without impaired spatial learning or memory...
December 9, 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27904491/intravenous-transplantation-of-mouse-embryonic-stem-cells-attenuates-demyelination-in-an-icr-outbred-mouse-model-of-demyelinating-diseases
#16
Kidsadagon Pringproa, Anucha Sathanawongs, Chananthida Khamphilai, Sarocha Sukkarinprom, Apichart Oranratnachai
Induction of demyelination in the central nervous system (CNS) of experimental mice using cuprizone is widely used as an animal model for studying the pathogenesis and treatment of demyelination. However, different mouse strains used result in different pathological outcomes. Moreover, because current medicinal treatments are not always effective in multiple sclerosis patients, so the study of exogenous cell transplantation in an animal model is of great importance. The aims of the present study were to establish an alternative ICR outbred mouse model for studying demyelination and to evaluate the effects of intravenous cell transplantation in the present developed mouse model...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27894396/ellagic-acid-ameliorates-cuprizone-induced-acute-cns-inflammation-via-restriction-of-microgliosis-and-down-regulation-of-ccl2-and-ccl3-pro-inflammatory-chemokines
#17
N Sanadgol, F Golab, A Mostafaie, M Mehdizadeh, M Abdollahi, M Sharifzadeh, H Ravan
Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuro-inflammatory conditions. Microglia making the innate immune system of the central nervous system (CNS) and are imperative cellular mediators of neuro-inflammatory processes. In this study, neuro-protective effects of EA on cuprizone (Cup)-induced acute CNS inflammation evaluated. C57BL/6J mice were fed with chow containing 0.2 % Cup for 3 weeks to induce acute neuro-inflammation predominantly in the corpus callosum (CC)...
October 31, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/27873367/mir-219-attenuates-demyelination-in-cuprizone-induced-demyelinated-mice-by-regulating-monocarboxylate-transporter-1
#18
Sihan Liu, Chuanlu Ren, Xuebin Qu, Xiuxiang Wu, Fuxing Dong, Yadav Kaushal Chand, Hongbin Fan, Ruiqin Yao, Deqin Geng
Remyelination is limited in patients with multiple sclerosis (MS) due to the difficulties in recruiting proliferating oligodendrocyte precursors (OPCs), the inhibition of OPC differentiation and/or maturation, and/or failure in the generation of the myelin sheath. In vitro studies have revealed that miR-219 is necessary for OPC differentiation and monocarboxylate transporter 1 (MCT1) plays a vital role in oligodendrocyte maturation and myelin synthesis. Herein, we hypothesized that miR-219 might promote oligodendrocyte differentiation and attenuate demyelination in a cuprizone (CPZ)-induced demyelinated model by regulating the expression of MCT1...
January 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27861886/oligodendrocyte-progenitor-cells-directly-utilize-lactate-for-promoting-cell-cycling-and-differentiation
#19
Yoshinori Ichihara, Toru Doi, Youngjae Ryu, Motoshi Nagao, Yasuhiro Sawada, Toru Ogata
Oligodendrocyte progenitor cells (OPCs) undergo marked morphological changes to become mature oligodendrocytes, but the metabolic resources for this process have not been fully elucidated. Although lactate, a metabolic derivative of glycogen, has been reported to be consumed in oligodendrocytes as a metabolite, and to ameliorate hypomyelination induced by low glucose conditions, it is not clear about the direct contribution of lactate to cell cycling and differentiation of OPCs, and the source of lactate for remyelination...
May 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27845252/the-connectomics-of-brain-demyelination-functional-and-structural-patterns-in-the-cuprizone-mouse-model
#20
Neele S Hübner, Anna E Mechling, Hsu-Lei Lee, Marco Reisert, Thomas Bienert, Jürgen Hennig, Dominik von Elverfeldt, Laura-Adela Harsan
Connectomics of brain disorders seeks to reveal how altered brain function emerges from the architecture of cerebral networks; however the causal impact of targeted cellular damage on the whole brain functional and structural connectivity remains unknown. In the central nervous system, demyelination is typically the consequence of an insult targeted at the oligodendrocytes, the cells forming and maintaining the myelin. This triggered perturbation generates cascades of pathological events that most likely alter the brain connectome...
February 1, 2017: NeuroImage
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