Read by QxMD icon Read


N K Singhal, K Alkhayer, J Shelestak, R Clements, E Freeman, J McDonough
Multiple sclerosis (MS) is a neuro-inflammatory and demyelinating disease. Downregulation of neuronal mitochondrial gene expression and activity have been reported in several studies of MS. We have previously shown that hemoglobin-β (Hbb) signals to the nucleus of neurons and upregulates H3K4me3, a histone mark involved in regulating cellular metabolism and differentiation. The present study was undertaken to evaluate the effect of erythropoietin (EPO) on the upregulation of hemoglobin and mitochondrial-associated neuroprotection...
March 1, 2018: Molecular Neurobiology
E Varga, E Pandur, H Abrahám, A Horváth, P Ács, S Komoly, A Miseta, K Sipos
Cuprizone (CZ) is a widely used copper chelating agent to develop non-autoimmune animal model of multiple sclerosis, characterized by demyelination of the corpus callosum (CC) and other brain regions. The exact mechanisms of CZ action are still arguable, but it seems that the only affected cells are the mature oligodendrocytes, possibly via metabolic disturbances caused by copper deficiency. During the pathogenesis of multiple sclerosis, high amount of deposited iron can be found throughout the demyelinated areas of the brain in the form of extracellular iron deposits and intracellularly accumulated iron in microglia...
February 20, 2018: Cellular and Molecular Neurobiology
Wataru Kojima, Kensuke Hayashi
Demyelination induced by cuprizone in mice has served a useful model system for the study of demyelinating diseases, such as multiple sclerosis. Severity of demyelination by cuprizone, however, varies across different regions of the central nervous system; the corpus callosum is sensitive, while the optic nerves are resistant. Here, we investigated the effects of cuprizone on optic nerves, focusing on the axo-glial junctions. Immunostaining for sodium channels, contactin-associated protein, neurofascins, and potassium channels revealed that there were no massive changes in the density and morphology of the axo-glial junctions in cuprizone-treated optic nerves...
February 19, 2018: Histochemistry and Cell Biology
Nicolau Beckmann, Elisa Giorgetti, Anna Neuhaus, Stefan Zurbruegg, Nathalie Accart, Paul Smith, Julien Perdoux, Ludovic Perrot, Mark Nash, Sandrine Desrayaud, Peter Wipfli, Wilfried Frieauff, Derya R Shimshek
Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system (CNS). While multiple effective immunomodulatory therapies for MS exist today, they lack the scope of promoting CNS repair, in particular remyelination. Microglia play a pivotal role in regulating myelination processes, and the colony-stimulating factor 1 (CSF-1) pathway is a key regulator for microglia differentiation and survival. Here, we investigated the effects of the CSF-1 receptor kinase inhibitor, BLZ945, on central myelination processes in the 5-week murine cuprizone model by non-invasive and longitudinal magnetic resonance imaging (MRI) and histology...
February 15, 2018: Acta Neuropathologica Communications
Giusy T Coppolino, Davide Marangon, Camilla Negri, Gianluca Menichetti, Marta Fumagalli, Paolo Gelosa, Leda Dimou, Roberto Furlan, Davide Lecca, Maria P Abbracchio
Promoting remyelination is recognized as a novel strategy to foster repair in neurodegenerative demyelinating diseases, such as multiple sclerosis. In this respect, the receptor GPR17, recently emerged as a new target for remyelination, is expressed by early oligodendrocyte precursors (OPCs) and after a certain differentiation stage it has to be downregulated to allow progression to mature myelinating oligodendrocytes. Here, we took advantage of the first inducible GPR17 reporter mouse line (GPR17-iCreERT2 xCAG-eGFP mice) allowing to follow the final fate of GPR17+ cells by tamoxifen-induced GFP-labeling to unveil the destiny of these cells in two demyelination models: experimental autoimmune encephalomyelitis (EAE), characterized by marked immune cell activation and inflammation, and cuprizone induced demyelination, where myelin dysfunction is achieved by a toxic insult...
February 9, 2018: Glia
Yu-E Guo, Na Suo, Xue Cui, Qianting Yuan, Xin Xie
Oligodendrocyte-formed myelin sheaths play important roles in the neuronal functions in the central nervous system. In demyelinating diseases, such as Multiple Sclerosis, the myelin sheaths are damaged and the remyelinating process is somehow hindered. Restoration of the myelin sheaths requires the differentiation of the oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs). To discover small molecule compounds that might promote the OPC to OL differentiation, a high-throughput screening system is established and L-ascorbyl-2-phosphate (As-2P), a stable form of Vitamin C (Vc), is found to greatly enhance the OPC to OL differentiation...
February 9, 2018: Glia
Ryoko Tsukahara, Shinji Yamamoto, Keisuke Yoshikawa, Mari Gotoh, Tamotsu Tsukahara, Hiroyuki Neyama, Satoshi Ishii, Noriyuki Akahoshi, Keisuke Yanagida, Hayakazu Sumida, Masatake Araki, Kimi Araki, Ken-Ichi Yamamura, Kimiko Murakami-Murofushi, Hiroshi Ueda
Lysophosphatidic acid (LPA) and LPA1 receptor signaling play a crucial role in the initiation of peripheral nerve injury-induced neuropathic pain through the alternation of pain-related genes/proteins expression and demyelination. However, LPA and its signaling in the brain are still poorly understood. In the present study, we revealed that the LPA5 receptor expression in corpus callosum elevated after the initiation of demyelination, and the hyperalgesia through Aδ-fibers following cuprizone-induced demyelination was mediated by LPA5 signaling...
February 2, 2018: Journal of Pharmacological Sciences
Mohsen Marzban, Kazem Mousavizadeh, Masoomeh Bakhshayesh, Nasim Vousooghi, Gelareh Vakilzadeh, Anahita Torkaman-Boutorabi
Background: Bone marrow mesenchymal stem cells (BM-MSCs) elicit neuroprotective effects, and their repair ability has been investigated in different experimental models. We aimed to investigate the effect of multiple i.p. BM-MSCs injections in the cuprizone model of multiple sclerosis in mice. Methods: Adult male C57BL/6 mice (n = 40) were fed a regular diet or a diet containing cuprizone (0.2% w/w) for 6 six weeks. Bone marrow samples were taken from patients with spinal cord injury...
February 7, 2018: Iranian Biomedical Journal
Nima Sanadgol, Fereshteh Golab, Ali Mostafaie, Mehdi Mehdizadeh, Roghayeh Khalseh, Morteza Mahmoudi, Mohammad Abdollahi, Gelareh Vakilzadeh, Ghorban Taghizadeh, Mohammad Sharifzadeh
Cuprizone (Cup) is a copper chelating agent frequently used to study factors that affect oligodendrocytes (OLGs) death and acute demyelination. Triptolide (TP), a nuclear factor-kappaB (NF-κB) blocker, is a major bioactive component of Tripterygium wilfordii Hook f. (TWHf) with various therapeutic activities. In this study, we examined the effects of TP on neuroglia activation, inflammation, apoptosis, demyelination, and behavioral deficits in the Cup-induced toxic model of multiple sclerosis (MS). C57BL/6 J mice were fed with chow containing 0...
January 31, 2018: Toxicology and Applied Pharmacology
Daisuke Fukudome, Lindsay N Hayes, Travis E Faust, Catherine A Foss, Mari A Kondo, Brian J Lee, Atsushi Saito, Shin-Ichi Kano, Jennifer M Coughlin, Atsushi Kamiya, Martin G Pomper, Akira Sawa, Minae Niwa
Changes in inflammatory cascades have been implicated in the underlying pathophysiology of psychosis. Translocator protein 18 kDa (TSPO) has been used to assess neuroinflammatory processes in psychotic disorders. Nonetheless, it is unclear whether TSPO, a mitochondrial protein, can be interpreted as a general marker for inflammation in diseases involving psychosis. To address this question, we investigated TSPO signaling in representative mouse models for psychosis with inflammatory disturbances. The maternal immune activation and cuprizone short-term exposure models show different TSPO signaling...
February 2, 2018: Schizophrenia Research
Pramod Kumar, Gajanand Sharma, Varun Gupta, Ramanpreet Kaur, Kanika Thakur, Ruchi Malik, Anil Kumar, Naveen Kaushal, Kaisar Raza
Multiple sclerosis (MS) is a neurodegenerative disease, where myelin sheath damage occurs due to internal and external factors and it affects especially young population. Dimethyl fumarate (DMF) is a promising agent for MS though associated with concerns like poor brain permeation, multiple dosing and gastro intestinal flushing. The present study attempts to evaluate preclinical performance of specially-designed DMF-based lipoidal-nanoparticles in cuprizone-induced demyelination rodent model. The studies proved the efficacy of lipid-based nanoparticles, containing DMF in once-a-day dosage regimen, over thrice-a-day plain DMF administration on the crucial parameters like motor coordination, grip strength, mortality, body weight and locomotor activity...
January 22, 2018: ACS Chemical Neuroscience
Yoshibumi Shimizu, Masaki Ishikawa, Mari Gotoh, Keiko Fukasawa, Shinji Yamamoto, Kensuke Iwasa, Keisuke Yoshikawa, Kimiko Murakami-Murofushi
Cyclic phosphatidic acid (cPA), an analog of lysophosphatidic acid, is involved in the regulation of many cellular processes. A sensitive and specific method to quantify the molecular species of cPA is important for studying the physiological and pathophysiological roles of cPA. Here, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based quantification method for the simultaneous detection of cPA species having various fatty acids (16:0, 18:0, 18:1, and 18:2) as well as 2-carba-cPA, a chemically synthesized analog of cPA...
January 8, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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
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
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
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
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
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...
March 2018: Glia
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
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
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"