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https://www.readbyqxmd.com/read/29142736/strain-differences-in-cuprizone-induced-demyelination
#1
Qili Yu, Ryan Hui, Jiyoung Park, Yangyang Huang, Alexander W Kusnecov, Cheryl F Dreyfus, Renping Zhou
Background: Multiple sclerosis (MS) is a severe neurological disorder, characterized by demyelination of the central nervous system (CNS), and with a prevalence of greater than 2 million people worldwide. In terms of research in MS pathology, the cuprizone toxicity model is widely used. Here we investigated the contribution of genetic differences in response to cuprizone-induced demyelination in two genetically different mouse strains: CD1 and C57BL/6. Results: We demonstrate that exposure to a diet containing 0...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29114910/n-acetylcysteine-attenuates-the-cuprizone-induced-behavioral-changes-and-oligodendrocyte-loss-in-male-c57bl-7-mice-via-its-anti-inflammation-actions
#2
Lin Zhang, Shuqin Xu, Qingjun Huang, Haiyun Xu
Previous animal studies have linked white matter damage to certain schizophrenia-like behaviors in cuprizone (CPZ)-exposed mouse. Mitochondrial dysfunction, oxidative stress, neuroinflammation, and oligodendrocyte loss coexist in the brain of such mice. The aim of this study was to examine effects of the antioxidant N-acetylcysteine (NAC) on CPZ-induced behavioral changes and concurrent oligodendrocyte loss, oxidative stress, and neuroinflammation in these animals. Male C57BL/6 mice were given intraperitoneal saline or NAC at doses of 100, 200, and 400 mg/kg/day for 2 weeks; animals were fed a CPZ-containing diet (0...
November 8, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29070438/humanin-affects-object-recognition-and-gliosis-in-short-term-cuprizone-treated-mice
#3
Minetaka Murakami, Masatoshi Nagahama, Yoichiro Abe, Takako Niikura
Humanin (HN) is a 24-residue peptide that manipulates cell survival under various stresses. A highly potent HN derivative, HNG, reduced amyloid burden and neuroinflammation and suppressed cognitive impairment in Alzheimer's disease model mice. Cuprizone (CPZ), a copper chelator, provokes demyelination in the central nervous system of mice. A shorter (one week) exposure to CPZ induces schizophrenia-like behavior and glial activation prior to demyelination. We tested the effect of HNG on these short-term responses to CZP in mice...
October 14, 2017: Neuropeptides
https://www.readbyqxmd.com/read/29045809/postnatal-sonic-hedgehog-shh-responsive-cells-give-rise-to-oligodendrocyte-lineage-cells-during-myelination-and-in-adulthood-contribute-to-remyelination
#4
Maria A Sanchez, Regina C Armstrong
Sonic hedgehog (Shh) regulates a wave of oligodendrocyte production for extensive myelination during postnatal development. During this postnatal period of oligodendrogenesis, we fate-labeled cells exhibiting active Shh signaling to examine their contribution to the regenerative response during remyelination. Bitransgenic mouse lines were generated for induced genetic fate-labeling of cells actively transcribing Shh or Gli1. Gli1 transcription is an effective readout for canonical Shh signaling. Shh(CreERT2) mice and Gli1(CreERT2) mice were crossed to either R26(tdTomato) mice to label cells with red fluorescence, or, R26(IAP) mice to label membranes with alkaline phosphatase...
October 16, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29038005/prednisone-alleviates-demyelination-through-regulation-of-the-nlrp3-inflammasome-in-a-c57bl-6-mouse-model-of-cuprizone-induced-demyelination
#5
Hao Yu, Mingfeng Wu, Geng Lu, Tingting Cao, Nan Chen, Yijia Zhang, Higuo Jiang, Hongbin Fan, Ruiqin Yao
Myelin abnormalities, oligodendrocyte damage, and concomitant glia activation are common in demyelinating diseases of the central nervous system (CNS). Increasing evidence has demonstrated that the inflammatory response triggers demyelination and gliosis in demyelinating disorders. Numerous clinical interventions, including those used to treat multiple sclerosis (MS), have confirmed prednisone (PDN) as a powerful anti-inflammatory drug that reduces the inflammatory response and promotes tissue repair in multiple inflammation sites...
October 13, 2017: Brain Research
https://www.readbyqxmd.com/read/29030079/quantitative-temporal-changes-in-dti-values-coupled-with-histological-properties-in-cuprizone-induced-demyelination-and-remyelination
#6
Ryutaro Yano, Junichi Hata, Yoshifumi Abe, Fumiko Seki, Keitaro Yoshida, Yuji Komaki, Hideyuki Okano, Kenji F Tanaka
Diffusion tensor imaging (DTI) is widely used to evaluate microstructural variations in brain tissue. In particular, fractional anisotropy (FA), reflecting the magnitude and orientation of anisotropic water diffusion, allows us to detect pathological events in white matter. An ex vivo DTI study coupled with histological assessment is an efficient strategy to evaluate the myelination process, i.e. demyelination and remyelination. The relationship between DTI values and myelin content or the individual cellular components such as oligodendrocytes, microglia, and astrocytes during both processes of demyelination and remyelination are not well-understood...
October 10, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29022246/alpha-lipoic-acid-mitigates-toxic-induced-demyelination-in-the-corpus-callosum-by-lessening-of-oxidative-stress-and-stimulation-of-polydendrocytes-proliferation
#7
Nima Sanadgol, Fereshteh Golab, Hassan Askari, Fatemeh Moradi, Marziyeh Ajdary, Mehdi Mehdizadeh
Multiple Sclerosis (MS), is a disease that degenerates myelin in central nervous system (CNS). Reactive oxygen species (ROSs) are toxic metabolites, and accumulating data indicate that ROSs-mediated apoptosis of oligodendrocytes (OLGs) plays a major role in the pathogenesis of MS under oxidative stress conditions. In this study, we investigated the role of endogenous antioxidant alpha-lipoic acid (ALA) as ROSs scavenger in the OLGs loss and myelin degeneration during cuprizone (cup)-induced demyelination in the experimental model of MS...
October 12, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28989170/olig2-silence-ameliorates-cuprizone-induced-schizophrenia-like-symptoms-in-mice
#8
Hongxia Liu, Jinguo Zhai, Bin Wang, Maosheng Fang
BACKGROUND The pathogenesis of schizophrenia is complex and oligodendrocyte abnormality is an important component of the pathogenesis found in schizophrenia. This study was designed to evaluate the function of olig2 in cuprizone-induced schizophrenia-like symptoms in a mouse model, and to assess the related mechanisms. MATERIAL AND METHODS The schizophrenia-like symptoms were modeled by administration of cuprizone in mice. Open-field and elevated-plus maze tests were applied to detect behavioral changes. Adenovirus encoding olig2 siRNA was designed to silence olig2 expression...
October 9, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28986688/unconventional-myosin-id-is-involved-in-remyelination-after-cuprizone-induced-demyelination
#9
Reiji Yamazaki, Hiroko Baba, Yoshihide Yamaguchi
Myelin, which is a multilamellar structure that sheathes the axon, is essential for normal neuronal function. In the central nervous system (CNS), myelin is produced by oligodendrocytes (OLs), which wrap their plasma membrane around axons. The dynamic membrane trafficking system, which relies on motor proteins, is required for myelin formation and maintenance. Previously, we reported that myosin ID (Myo1d) is distributed in rat CNS myelin and is especially enriched in the outer and inner cytoplasm-containing loops...
October 6, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28984112/effects-of-green-tea-epigallocatechin-3-gallate-on-the-proteolipid-protein-and-oligodendrocyte-transcription-factor-1-messenger-rna-gene-expression-in-a-mouse-model-of-multiple-sclerosis
#10
Mohammadreza Semnani, Farhad Mashayekhi, Mahnaz Azarnia, Zivar Salehi
The cuprizone multiple sclerosis (MS) animal model is characteristic for toxic demyelination and represents a reversible demyelination and remyelination system. It has been shown that green tea epigallocatechin-3-gallate (EGCG) might be effective in improving the symptoms and pathological conditions associated with autoimmune inflammatory diseases in several animal models. In this study the effects of EGCG on proteolipid protein (PLP) and oligodendrocyte transcription factor 1 (Olig1) expression in the cerebral cortex of a murine model of cuprizone-induced demyelination was investigated...
2017: Folia Neuropathologica
https://www.readbyqxmd.com/read/28940645/lineage-tracing-reveals-dynamic-changes-in-oligodendrocyte-precursor-cells-following-cuprizone-induced-demyelination
#11
Emily G Baxi, Joseph DeBruin, Jing Jin, Hayley J Strasburger, Matthew D Smith, Jennifer L Orthmann-Murphy, Jason T Schott, Amanda N Fairchild, Dwight E Bergles, Peter A Calabresi
The regeneration of oligodendrocytes is a crucial step in recovery from demyelination, as surviving oligodendrocytes exhibit limited structural plasticity and rarely form additional myelin sheaths. New oligodendrocytes arise through the differentiation of platelet-derived growth factor receptor α (PDGFRα) expressing oligodendrocyte progenitor cells (OPCs) that are widely distributed throughout the CNS. Although there has been detailed investigation of the behavior of these progenitors in white matter, recent studies suggest that disease burden in multiple sclerosis (MS) is more strongly correlated with gray matter atrophy...
September 22, 2017: Glia
https://www.readbyqxmd.com/read/28929408/yokukansan-reduces-cuprizone-induced-demyelination-in-the-corpus-callosum-through-anti-inflammatory-effects-on-microglia
#12
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
#13
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...
December 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
#14
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 18, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28923306/the-flavonoid-baicalein-attenuates-cuprizone-induced-demyelination-via-suppression-of-neuroinflammation
#15
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 antioxidant effects. The cuprizone model is an established mouse model of MS and causes demyelination and motor dysfunction and induces 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
#16
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
#17
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...
October 11, 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
#18
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 developing 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 generated an inducible conditional knock-out mouse in which the L-VGCC isoform Cav1.2 was deleted in NG2-positive OPCs (Cav1.2(KO))...
October 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28863829/experimental-models-of-demyelination-and-remyelination
#19
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
#20
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 express IFN-γ ectopically in the CNS (both sexes)...
September 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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