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https://www.readbyqxmd.com/read/28929408/yokukansan-reduces-cuprizone-induced-demyelination-in-the-corpus-callosum-through-anti-inflammatory-effects-on-microglia
#1
Taichi Nomura, Yoshio Bando, Hua You, Tatsuhide Tanaka, Shigetaka Yoshida
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). The release of inflammatory cytokines and pro-oxidant molecules from microglia has been shown to play a key role in the pathology of MS. Thus, suppression of microglial cell activation is an attractive therapeutic option. Yokukansan, a traditional Japanese herbal medicine, has been shown to suppress microglial activity in the CNS. However, whether or not yokukansan reduces demyelination observed in the CNS during MS remains unknown...
September 19, 2017: Neurochemical Research
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/28911344/comparison-of-spectrophotometric-methods-for-the-determination-of-copper-in-sugar-cane-spirit
#5
Sarah Adriana R Soares, Silvânio Silvério L Costa, Rennan Geovanny O Araujo, Leonardo Sena Gomes Teixeira, Alailson Falcão Dantas
Three spectrophotometric methods were developed for the determination of copper (Cu) in sugar cane spirit using the chromogenic reagents neocuproine, cuprizone, and bathocuproine. Experimental conditions, such as reagent concentration, reducer concentration, pH, buffer concentration, the order of addition of reagents, and the stability of the complexes, were optimized. The work range was established from 1.0 to 10.0 µg/mL, with correlation coefficients of >0.999 for all three optimized methods. The methods were evaluated regarding accuracy by addition and recovery tests at five concentration levels, and the obtained recoveries ranged from 91 to 105% (n = 3)...
September 15, 2017: Journal of AOAC International
https://www.readbyqxmd.com/read/28899916/gd1a-overcomes-inhibition-of-myelination-by-fibronectin-via-activation-of-protein-kinase-a-implications-for-multiple-sclerosis
#6
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
#7
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/28863829/experimental-models-of-demyelination-and-remyelination
#8
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
#9
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
#10
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/28836302/combination-of-cuprizone-and-experimental-autoimmune-encephalomyelitis-to-study-inflammatory-brain-lesion-formation-and-progression
#11
Bernhard Josef Rüther, Miriam Scheld, Daniela Dreymueller, Tim Clarner, Eugenia Kress, Lars-Ove Brandenburg, Tine Swartenbroekx, Chloé Hoornaert, Peter Ponsaerts, Petra Fallier-Becker, Cordian Beyer, Sven Olaf Rohr, Christoph Schmitz, Uta Chrzanowski, Tanja Hochstrasser, Stella Nyamoya, Markus Kipp
Brain-intrinsic degenerative cascades are a proposed factor driving inflammatory lesion formation in multiple sclerosis (MS) patients. We recently described a model combining noninflammatory cytodegeneration (via cuprizone) with the classic active experimental autoimmune encephalomyelitis (Cup/EAE model), which exhibits inflammatory forebrain lesions. Here, we describe the histopathological characteristics and progression of these Cup/EAE lesions. We show that inflammatory lesions develop at various topographical sites in the forebrain, including white matter tracts and cortical and subcortical grey matter areas...
August 24, 2017: Glia
https://www.readbyqxmd.com/read/28830026/progesterone-therapy-induces-an-m1-to-m2-switch-in-microglia-phenotype-and-suppresses-nlrp3-inflammasome-in-a-cuprizone-induced-demyelination-mouse-model
#12
Roya Aryanpour, Parichehr Pasbakhsh, Kazem Zibara, Zeinab Namjoo, Fatemeh Beigi Boroujeni, Saeed Shahbeigi, Iraj Ragerdi Kashani, Cordian Beyer, Adib Zendehdel
Demyelination of the central nervous system (CNS) has been associated to reactive microglia in neurodegenerative disorders, such as multiple sclerosis (MS). The M1 microglia phenotype plays a pro-inflammatory role while M2 is involved in anti-inflammatory processes in the brain. In this study, CPZ-induced demyelination mouse model was used to investigate the effect of progesterone (PRO) therapy on microglia activation and neuro-inflammation. Results showed that progesterone therapy (CPZ+PRO) decreased neurological behavioral deficits, as demonstrated by significantly decreased escape latencies, in comparison to CPZ mice...
August 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28828543/expression-of-unconventional-myosin-vi-in-oligodendrocytes
#13
Reiji Yamazaki, Tomoko Ishibashi, Hiroko Baba, Yoshihide Yamaguchi
Myelin is a specialized multilamellar structure involved in various functions of the nervous system. Oligodendrocytes are responsible for myelin formation in the central nervous system. Motor proteins play important roles in differentiation and myelin formation of the oligodendrocyte lineage. Recently, we revealed that one of the unconventional myosins, myosin ID (Myo1d), is expressed in mature oligodendrocytes and is required for myelin-like membrane formation in vitro. Previously, Cahoy et al. (J Neurosci 28:264-278, 2008) reported that another unconventional myosin VI (Myo6) is upregulated in transcriptome data of differentiated oligodendrocytes...
August 21, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28821276/inflammatory-demyelination-alters-subcortical-visual-circuits
#14
Sheila Espírito Santo Araújo, Henrique Rocha Mendonça, Natalie A Wheeler, Paula Campello-Costa, Kimberle M Jacobs, Flávia C A Gomes, Michael A Fox, Babette Fuss
BACKGROUND: Multiple sclerosis (MS) is an inflammatory demyelinating disease classically associated with axonal damage and loss; more recently, however, synaptic changes have been recognized as additional contributing factors. An anatomical area commonly affected in MS is the visual pathway; yet, changes other than those associated with inflammatory demyelination of the optic nerve, i.e., optic neuritis, have not been described in detail. METHODS: Adult mice were subjected to a diet containing cuprizone to mimic certain aspects of inflammatory demyelination as seen in MS...
August 18, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28818673/1-25-dihydroxyvitamin-d3-induces-brain-proteomic-changes-in-cuprizone-mice-during-remyelination-involving-calcium-proteins
#15
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/28783571/a-novel-flavanone-derivative-ameliorates-cuprizone-induced-behavioral-changes-and-white-matter-pathology-in-the-brain-of-mice
#16
Zheng-Yu Sun, Hong-Shun Gu, Xi Chen, Lan Zhang, Xin-Min Li, Jian-Wei Zhang, Lin Li
Recent studies have shown that white matter lesions play an important role in the pathogenesis of schizophrenia. DHF-6 is a novel flavanone derivative synthesized in our laboratory. The purpose of the present study was to investigate the effects of DHF-6 on behavioral changes and white matter pathology in a 0.2% cuprizone-fed C57BL/6 mice model. The results showed that cuprizone induced a decrease in spontaneous alternations in the Y-maze test, an increase in locomotor activity in the open field test, demyelination determined by electron microscopy, a decline in the expression of myelin basic protein (MBP), a decrease in the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs), and an activation of microglia and astrocytes in the corpus callosum measured by western blot and/or immunocytochemical analyses...
July 31, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28760957/hyperpolarized-13-c-mr-metabolic-imaging-can-detect-neuroinflammation-in-vivo-in-a-multiple-sclerosis-murine-model
#17
Caroline Guglielmetti, Chloé Najac, Alessandro Didonna, Annemie Van der Linden, Sabrina M Ronen, Myriam M Chaumeil
Proinflammatory mononuclear phagocytes (MPs) play a crucial role in the progression of multiple sclerosis (MS) and other neurodegenerative diseases. Despite advances in neuroimaging, there are currently limited available methods enabling noninvasive detection of MPs in vivo. Interestingly, upon activation and subsequent differentiation toward a proinflammatory phenotype MPs undergo metabolic reprogramming that results in increased glycolysis and production of lactate. Hyperpolarized (HP) (13)C magnetic resonance spectroscopic imaging (MRSI) is a clinically translatable imaging method that allows noninvasive monitoring of metabolic pathways in real time...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28760868/polysialylation-at-early-stages-of-oligodendrocyte-differentiation-promotes-myelin-repair
#18
Sebastian Werneburg, Hazel L S Fuchs, Iris Albers, Hannelore Burkhardt, Viktoria Gudi, Thomas Skripuletz, Martin Stangel, Rita Gerardy-Schahn, Herbert Hildebrandt
Polysialic acid is a glycan modification of the neural cell adhesion molecule (NCAM) produced by the polysialyltransferases ST8SIA2 and ST8SIA4. Polysialic acid has been detected in multiple sclerosis plaques, but its beneficial or adverse role in remyelination is elusive. Here, we show that, despite a developmental delay, myelination at the onset and during cuprizone-induced demyelination was unaffected in male Ncam1(-/-) or St8sia2(-/-) mice. However, remyelination, restoration of oligodendrocyte densities, and motor recovery after the cessation of cuprizone treatment were compromised...
August 23, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28757612/the-cd24-siglec-g-axis-protects-mice-against-cuprizone-induced-oligodendrocyte-loss-targeting-danger-signal-for-neuroprotection
#19
Ning Li, Pan Zheng, Yang Liu
No abstract text is available yet for this article.
July 31, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28732510/protective-and-therapeutic-role-of-2-carba-cyclic-phosphatidic-acid-in-demyelinating-disease
#20
Shinji Yamamoto, Kota Yamashina, Masaki Ishikawa, Mari Gotoh, Sosuke Yagishita, Kensuke Iwasa, Kei Maruyama, Kimiko Murakami-Murofushi, Keisuke Yoshikawa
BACKGROUND: Multiple sclerosis is a neuroinflammatory demyelinating and neurodegenerative disease of the central nervous system characterized by recurrent and progressive demyelination/remyelination cycles, neuroinflammation, oligodendrocyte loss, demyelination, and axonal degeneration. Cyclic phosphatidic acid (cPA) is a natural phospholipid mediator with a unique cyclic phosphate ring structure at the sn-2 and sn-3 positions of the glycerol backbone. We reported earlier that cPA elicits a neurotrophin-like action and protects hippocampal neurons from ischemia-induced delayed neuronal death...
July 21, 2017: Journal of Neuroinflammation
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