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https://www.readbyqxmd.com/read/29325992/quantitative-analysis-of-lipid-debris-accumulation-caused-by-cuprizone-induced-myelin-degradation-in-different-cns-areas
#1
Attila Ozsvár, Róbert Szipőcs, Zoltán Ozsvár, Judith Baka, Pál Barzó, Gábor Tamás, Gábor Molnár
Degradation of myelin sheath is thought to be the cause of neurodegenerative diseases, such as multiple sclerosis (MS), but definitive agreement on mechanism of how myelin is lost is currently lacking. Autoimmune initiation of MS has been recently questioned by proposing that the immune response is a consequence of oligodendrocyte degeneration. To study the process of myelin breakdown, we induced demyelination with cuprizone and applied coherent anti-Stokes Raman scattering (CARS) microscopy, a non-destructive label-free method to image lipid structures in living tissue...
January 8, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29288338/toll-like-receptor-2-mediated-glial-cell-activation-in-a-mouse-model-of-cuprizone-induced-demyelination
#2
Stefan Esser, Larissa Göpfrich, Kai Bihler, Eugenia Kress, Stella Nyamoya, Simone C Tauber, Tim Clarner, Matthias B Stope, Thomas Pufe, Markus Kipp, 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. The factors triggering gliosis and demyelination are currently not well characterized. New findings suggest an important role of the innate immune response in the initiation and progression of active demyelinating lesions. Especially during progressive disease, aberrant glia activation rather than the invasion of peripheral immune cells is accountable for progressive neuronal injury...
December 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29216327/protamine-neutralizes-chondroitin-sulfate-proteoglycan-mediated-inhibition-of-oligodendrocyte-differentiation
#3
Kazuya Kuboyama, Naomi Tanga, Ryoko Suzuki, Akihiro Fujikawa, Masaharu Noda
Chondroitin sulfate proteoglycans (CSPGs), which are enriched in demyelinating plaques in neurodegenerative diseases, such as multiple sclerosis (MS), impair remyelination by inhibiting the migration and differentiation of oligodendrocyte precursor cells (OPCs) in the central nervous system (CNS). We herein show that protamine (PRM, also known as a heparin antagonist) effectively neutralizes the inhibitory activities of CSPGs, thereby enhancing OPC differentiation and (re)myelination in mice. Cell-based assays using mouse OPC-like OL1 cells revealed that the PRM treatment exerted masking effects on extracellular CSPGs and improved oligodendrocyte differentiation on inhibitory CSPG-coated substrates...
2017: PloS One
https://www.readbyqxmd.com/read/29202545/mmp9-gene-expression-variation-by-ingesting-tart-cherry-and-p-coumaric-acid-during-remyelination-in-the-cuprizone-mouse-model
#4
Newshan Behrangi, Nabiyollah Namvar, Mitra Ataei, Sakineh Dizaji, Golshid Javdani, Mahommad Hossein Sanati
Matrix metalloproteinase-9 (GELB) as a member of gelatinases plays key role in the destruction of blood-brain barrier (BBB), T cells migration into the CNS, and demyelination induction. Considering remyelination induction in response to tart cherry extract and pure p-coumaric acid ingestion via tracking MMP9 gene expression in the cuprizone mouse model. Firstly, predicting the chemical interaction between p-coumaric acid and MMP9 protein was conducted through PASS and Swiss dock web services. Next, the content of p-coumaric acid in the tart cherry extract was analyzed by HPLC...
September 2017: Acta Medica Iranica
https://www.readbyqxmd.com/read/29195512/blood-brain-barrier-hyperpermeability-precedes-demyelination-in-the-cuprizone-model
#5
Stefan A Berghoff, Tim Düking, Lena Spieth, Jan Winchenbach, Sina K Stumpf, Nina Gerndt, Kathrin Kusch, Torben Ruhwedel, Wiebke Möbius, Gesine Saher
In neuroinflammatory disorders such as multiple sclerosis, the physiological function of the blood-brain barrier (BBB) is perturbed, particularly in demyelinating lesions and supposedly secondary to acute demyelinating pathology. Using the toxic non-inflammatory cuprizone model of demyelination, we demonstrate, however, that the onset of persistent BBB impairment precedes demyelination. In addition to a direct effect of cuprizone on endothelial cells, a plethora of inflammatory mediators, which are mainly of astroglial origin during the initial disease phase, likely contribute to the destabilization of endothelial barrier function in vivo...
December 1, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29193293/functional-antagonism-of-sphingosine-1-phosphate-receptor-1-prevents-cuprizone-induced-demyelination
#6
SunJa Kim, Jacek Bielawski, Hyunmin Yang, Yu Kong, Beiyan Zhou, Jianrong Li
Recent evidence suggests that the oral drug Fingolimod (FTY720) for relapsing-remitting multiple sclerosis (MS) may act directly on the central nervous system (CNS) and modulate disease pathogenesis and progression in experimental models of MS. However, the specific subtype of sphingosine-1-phosphate (S1P) receptors that mediates the effect of FTY720 on the CNS cells has not been fully elucidated. Here, we report that S1P receptor 1 (S1PR1) is elevated in reactive astrocytes in an autoimmunity independent mouse model of MS and that selective S1PR1 modulation is sufficient to ameliorate the loss of oligodendrocytes and demyelination...
November 29, 2017: Glia
https://www.readbyqxmd.com/read/29165835/the-function-of-contactin-2-tag-1-in-oligodendrocytes-in-health-and-demyelinating-pathology
#7
Lida Zoupi, Maria Savvaki, Katerina Kalemaki, Ilias Kalafatakis, Kyriaki Sidiropoulou, Domna Karagogeos
The oligodendrocyte maturation process and the transition from the pre-myelinating to the myelinating state are extremely important during development and in pathology. In the present study, we have investigated the role of the cell adhesion molecule CNTN2/TAG-1 on oligodendrocyte proliferation, differentiation, myelination, and function during development and under pathological conditions. With the combination of in vivo, in vitro, ultrastructural, and electrophysiological methods, we have mapped the expression of CNTN2 protein in the oligodendrocyte lineage during the different stages of myelination and its involvement on oligodendrocyte maturation, branching, myelin-gene expression, myelination, and axonal function...
November 22, 2017: Glia
https://www.readbyqxmd.com/read/29142736/strain-differences-in-cuprizone-induced-demyelination
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
December 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
#20
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
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