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[PMID]:29353671
[Au] Autor:Shimizu Y; Ishikawa M; Gotoh M; Fukasawa K; Yamamoto S; Iwasa K; Yoshikawa K; Murakami-Murofushi K
[Ad] Endereço:Endowed Research Division of Human Welfare Sciences, Ochanomizu University, Tokyo, Japan. Electronic address: y-shimuzu@lrc.or.jp.
[Ti] Título:Quantitative determination of cyclic phosphatidic acid and its carba analog in mouse organs and plasma using LC-MS/MS.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1076:15-21, 2018 Feb 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo: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. Chromatography was performed using a reversed-phase C18 column. cPA species were detected using a triple quadrupole mass spectrometer. cPA 17:0 was used as an internal standard. Intra- and interday precision values (CV%) were within 10%. The linear range of detection for each cPA species was 0.01 µg/mL to 5 µg/mL, with correlation coefficients of 0.998 or higher. The developed method was applied to the quantification of cPA species in mouse plasma and organs. The concentrations of cPA 16:0, 18:0, and 18:1 were revealed to be significantly reduced in the brains of cuprizone-treated mice, a model of multiple sclerosis, compared with control mice. These findings could be important for understanding the roles of cPA in the neurodegenerative processes associated with multiple sclerosis.
[Mh] Termos MeSH primário: Compostos Heterocíclicos com 1 Anel/análise
Ácidos Fosfatídicos/análise
[Mh] Termos MeSH secundário: Animais
Cromatografia Líquida/métodos
Cuprizona/efeitos adversos
Compostos Heterocíclicos com 1 Anel/metabolismo
Limite de Detecção
Modelos Lineares
Masculino
Camundongos
Esclerose Múltipla/induzido quimicamente
Esclerose Múltipla/metabolismo
Especificidade de Órgãos
Ácidos Fosfatídicos/metabolismo
Reprodutibilidade dos Testes
Espectrometria de Massas em Tandem/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-carba-cyclic phosphatidic acid); 0 (Heterocyclic Compounds, 1-Ring); 0 (Phosphatidic Acids); 0 (cyclic phosphatidic acid 16:0); 5N16U7E0AO (Cuprizone)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180123
[St] Status:MEDLINE


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[PMID]:28899916
[Au] Autor:Qin J; Sikkema AH; van der Bij K; de Jonge JC; Klappe K; Nies V; Jonker JW; Kok JW; Hoekstra D; Baron W
[Ad] Endereço:Department of Cell Biology, University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, The Netherlands, and.
[Ti] Título:GD1a Overcomes Inhibition of Myelination by Fibronectin via Activation of Protein Kinase A: Implications for Multiple Sclerosis.
[So] Source:J Neurosci;37(41):9925-9938, 2017 Oct 11.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo: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.e., cell surface lipids with a potential to modulate signaling pathways) could counteract fibronectin-mediated inhibition of OPC maturation. Exclusive exposure of rat oligodendrocytes to GD1a, but not other gangliosides, overcomes aggregated fibronectin-induced inhibition of myelin membrane formation, , and OPC differentiation in fibronectin aggregate containing cuprizone-induced demyelinated lesions in male mice. GD1a exerts its effect on OPCs by inducing their proliferation and, at a late stage, by modulating OPC maturation. Kinase activity profiling revealed that GD1a activated a protein kinase A (PKA)-dependent signaling pathway and increased phosphorylation of the transcription factor cAMP response element-binding protein. Consistently, the effect of GD1a in restoring myelin membrane formation in the presence of fibronectin aggregates was abolished by the PKA inhibitor H89, whereas the effect of GD1a was mimicked by the PKA activator dibutyryl-cAMP. Together, GD1a overcomes the inhibiting effect of aggregated fibronectin on OPC maturation by activating a PKA-dependent signaling pathway. Given the persistent presence of fibronectin aggregates in MS lesions, ganglioside GD1a might act as a potential novel therapeutic tool to selectively modulate the detrimental signaling environment that precludes remyelination. As an environmental factor, aggregates of the extracellular matrix protein fibronectin perturb the maturation of oligodendrocyte progenitor cells (OPCs), thereby impeding remyelination, in the demyelinating disease multiple sclerosis (MS). Here we demonstrate that exogenous addition of ganglioside GD1a overcomes the inhibiting effect of aggregated fibronectin on OPC maturation, both and , by activating a PKA-dependent signaling pathway. We propose that targeted delivery of GD1a to MS lesions may act as a potential novel molecular tool to boost maturation of resident OPCs to overcome remyelination failure and halt disease progression.
[Mh] Termos MeSH primário: Proteínas Quinases Dependentes de AMP Cíclico/metabolismo
Fibronectinas/antagonistas & inibidores
Gangliosídeos/farmacologia
Esclerose Múltipla/tratamento farmacológico
Esclerose Múltipla/patologia
Bainha de Mielina/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Axônios/efeitos dos fármacos
Axônios/patologia
Células Cultivadas
Cuprizona/toxicidade
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo
Doenças Desmielinizantes/induzido quimicamente
Doenças Desmielinizantes/prevenção & controle
Ativação Enzimática
Fibronectinas/farmacologia
Masculino
Camundongos
Bainha de Mielina/patologia
Células-Tronco Neurais/efeitos dos fármacos
Oligodendroglia/efeitos dos fármacos
Oligodendroglia/patologia
Ratos
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclic AMP Response Element-Binding Protein); 0 (Fibronectins); 0 (Gangliosides); 12707-58-3 (ganglioside, GD1a); 5N16U7E0AO (Cuprizone); EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170914
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.0103-17.2017


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[PMID]:28825598
[Au] Autor:Kuroda M; Muramatsu R; Maedera N; Koyama Y; Hamaguchi M; Fujimura H; Yoshida M; Konishi M; Itoh N; Mochizuki H; Yamashita T
[Ad] Endereço:Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
[Ti] Título:Peripherally derived FGF21 promotes remyelination in the central nervous system.
[So] Source:J Clin Invest;127(9):3496-3509, 2017 Sep 01.
[Is] ISSN:1558-8238
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Demyelination in the central nervous system (CNS) leads to severe neurological deficits that can be partially reversed by spontaneous remyelination. Because the CNS is isolated from the peripheral milieu by the blood-brain barrier, remyelination is thought to be controlled by the CNS microenvironment. However, in this work we found that factors derived from peripheral tissue leak into the CNS after injury and promote remyelination in a murine model of toxin-induced demyelination. Mechanistically, leakage of circulating fibroblast growth factor 21 (FGF21), which is predominantly expressed by the pancreas, drives proliferation of oligodendrocyte precursor cells (OPCs) through interactions with ß-klotho, an essential coreceptor of FGF21. We further confirmed that human OPCs expressed ß-klotho and proliferated in response to FGF21 in vitro. Vascular barrier disruption is a common feature of many CNS disorders; thus, our findings reveal a potentially important role for the peripheral milieu in promoting CNS regeneration.
[Mh] Termos MeSH primário: Sistema Nervoso Central/citologia
Fatores de Crescimento de Fibroblastos/fisiologia
Regeneração Nervosa/fisiologia
[Mh] Termos MeSH secundário: Animais
Barreira Hematoencefálica/metabolismo
Diferenciação Celular
Proliferação Celular
Sistema Nervoso Central/metabolismo
Cuprizona/química
Doenças Desmielinizantes/metabolismo
Feminino
Seres Humanos
Cinética
Proteínas de Membrana/metabolismo
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Esclerose Múltipla/metabolismo
Bainha de Mielina/metabolismo
Oligodendroglia/citologia
Permeabilidade
Medicina Regenerativa
Células-Tronco/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (KLB protein, human); 0 (Membrane Proteins); 0 (fibroblast growth factor 21); 5N16U7E0AO (Cuprizone); 62031-54-3 (Fibroblast Growth Factors)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170822
[St] Status:MEDLINE


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[PMID]:28778453
[Au] Autor:Petkovic F; Campbell IL; Gonzalez B; Castellano B
[Ad] Endereço:Department of Cell Biology, Physiology and Immunology, Institute of Neuroscience, Autonomous University of Barcelona, Bellaterra 08193, Spain; Department of Immunology, Institute for Biological Research "Sinisa Stankovic", 11000 Belgrade, Serbia. Electronic address: petkovicfilip@yahoo.com.
[Ti] Título:Reduced cuprizone-induced cerebellar demyelination in mice with astrocyte-targeted production of IL-6 is associated with chronically activated, but less responsive microglia.
[So] Source:J Neuroimmunol;310:97-102, 2017 Sep 15.
[Is] ISSN:1872-8421
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cerebellar pathology is a frequent feature of multiple sclerosis (MS), a demyelinating and neuroinflammatory disease of the central nervous system (CNS). Interleukin (IL)-6 is a multifunctional cytokine with a potential role in MS. Here we studied cuprizone-induced cerebellar pathology in transgenic mice with astrocyte-targeted production of IL-6 (GFAP-IL6), specifically focusing on demyelination, oligodendrocyte depletion and microglial cell response. RESULTS: Over the course of cuprizone treatment, when compared with WT mice, GFAP-IL6Tg showed a reduced demyelination in the deep lateral cerebellar nuclei (LCN). The oligodendrocyte numbers in the LCN were comparable between WT and GFAP-IL6Tg mice after 4-6weeks of cuprizone treatment, however after the chronic cuprizone treatment (12weeks) we detected higher numbers of oligodendrocytes in GFAP-IL6Tg mice. Contrary to strong cuprizone-induced microglial activation in the LCN of WT mice, GFAP-IL6Tg mice had minimal cuprizone-induced microglial changes, despite an already existing reactive microgliosis in control GFAP-IL6Tg not present in control WT mice. CONCLUSIONS: Our results show that chronic transgenic production of IL-6 reduced cuprizone-induced cerebellar demyelination and induced a specific activation state of the resident microglia population (Iba1 , CD11b , MHCII , CD68 ), likely rendering them less responsive to subsequent injury signals.
[Mh] Termos MeSH primário: Astrócitos/metabolismo
Cerebelo/patologia
Doenças Desmielinizantes/patologia
Interleucina-6/metabolismo
Microglia/metabolismo
[Mh] Termos MeSH secundário: Animais
Astrócitos/efeitos dos fármacos
Proteínas de Ligação ao Cálcio/metabolismo
Cuprizona/toxicidade
Citocinas/metabolismo
Doenças Desmielinizantes/induzido quimicamente
Modelos Animais de Doenças
Regulação da Expressão Gênica/efeitos dos fármacos
Regulação da Expressão Gênica/genética
Proteína Glial Fibrilar Ácida/genética
Proteína Glial Fibrilar Ácida/metabolismo
Interleucina-6/genética
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Proteínas dos Microfilamentos/metabolismo
Microglia/efeitos dos fármacos
Proteína Básica da Mielina/metabolismo
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aif1 protein, mouse); 0 (Calcium-Binding Proteins); 0 (Cytokines); 0 (Glial Fibrillary Acidic Protein); 0 (Interleukin-6); 0 (Mbp protein, mouse); 0 (Microfilament Proteins); 0 (Myelin Basic Protein); 5N16U7E0AO (Cuprizone)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170822
[Lr] Data última revisão:
170822
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170806
[St] Status:MEDLINE


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[PMID]:28582448
[Au] Autor:Chami M; Halmer R; Schnoeder L; Anne Becker K; Meier C; Fassbender K; Gulbins E; Walter S
[Ad] Endereço:Department of Neurology, Saarland University Hospital, Homburg, Germany.
[Ti] Título:Acid sphingomyelinase deficiency enhances myelin repair after acute and chronic demyelination.
[So] Source:PLoS One;12(6):e0178622, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The cuprizone animal model, also known as the toxic demyelination model, is a well-reproducible model of demyelination- and remyelination in mice, and has been useful in studying important aspect of human demyelinating diseases, including multiple sclerosis. In this study, we investigated the role of acid sphingomyelinase in demyelination and myelin repair by inducing acute and chronic demyelination with 5- or 12-week cuprizone treatment, followed by a 2-week cuprizone withdrawal phase to allow myelin repair. Sphingolipids, in particular ceramide and the enzyme acid sphingomyelinase, which generates ceramide from sphingomyelin, seem to be involved in astrocyte activation and neuronal damage in multiple sclerosis. We used immunohistochemistry to study glial reaction and oligodendrocyte distribution in acid sphingomyelinase deficient mice and wild-type C57BL/6J littermates at various time intervals after demyelination and remyelination. Axonal injury was quantified using amyloid precursor protein and synaptophysin, and gene expression and protein levels were measured using gene analysis and Western blotting, respectively. Our results show that mice lacking acid sphingomyelinase had a significant increase in myelin recovery and a significantly higher oligodendrocyte cell count after 2 weeks remyelination compared to wild-type littermates. Detrimental astroglial distribution was also significantly reduced in acid sphingomyelinase deficient animals. We obtained similar results in experiments using amitriptyline to inhibit acid sphingomyelinase. These findings suggest that acid sphingomyelinase plays a significant role in myelin repair, and its inhibition by amitriptyline may constitute a novel therapeutic approach for multiple sclerosis patients.
[Mh] Termos MeSH primário: Amitriptilina/farmacologia
Doenças Desmielinizantes/prevenção & controle
Inibidores Enzimáticos/farmacologia
Esclerose Múltipla/prevenção & controle
Oligodendroglia/efeitos dos fármacos
Esfingomielina Fosfodiesterase/genética
[Mh] Termos MeSH secundário: Secretases da Proteína Precursora do Amiloide/genética
Secretases da Proteína Precursora do Amiloide/metabolismo
Animais
Astrócitos/efeitos dos fármacos
Astrócitos/enzimologia
Astrócitos/patologia
Axônios/efeitos dos fármacos
Axônios/enzimologia
Axônios/patologia
Contagem de Células
Cuprizona
Doenças Desmielinizantes/induzido quimicamente
Doenças Desmielinizantes/enzimologia
Doenças Desmielinizantes/patologia
Modelos Animais de Doenças
Regulação da Expressão Gênica
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Microglia/efeitos dos fármacos
Microglia/enzimologia
Microglia/patologia
Esclerose Múltipla/induzido quimicamente
Esclerose Múltipla/enzimologia
Esclerose Múltipla/patologia
Regeneração Nervosa/efeitos dos fármacos
Oligodendroglia/enzimologia
Oligodendroglia/patologia
Recuperação de Função Fisiológica/efeitos dos fármacos
Esfingomielina Fosfodiesterase/antagonistas & inibidores
Esfingomielina Fosfodiesterase/deficiência
Sinaptofisina/genética
Sinaptofisina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Synaptophysin); 0 (Syp protein, mouse); 1806D8D52K (Amitriptyline); 5N16U7E0AO (Cuprizone); EC 3.1.4.- (acid sphingomyelinase-1); EC 3.1.4.12 (Sphingomyelin Phosphodiesterase); EC 3.4.- (Amyloid Precursor Protein Secretases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170606
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178622


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[PMID]:28447514
[Au] Autor:Sanadgol N; Golab F; Tashakkor Z; Taki N; Moradi Kouchi S; Mostafaie A; Mehdizadeh M; Abdollahi M; Taghizadeh G; Sharifzadeh M
[Ad] Endereço:a Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
[Ti] Título:Neuroprotective effects of ellagic acid on cuprizone-induced acute demyelination through limitation of microgliosis, adjustment of CXCL12/IL-17/IL-11 axis and restriction of mature oligodendrocytes apoptosis.
[So] Source:Pharm Biol;55(1):1679-1687, 2017 Dec.
[Is] ISSN:1744-5116
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:CONTEXT: Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuropathologic conditions. OBJECTIVE: In vivo neuroprotective effects of EA on cuprizone (cup)-induced demyelination were evaluated. MATERIAL AND METHODS: C57BL/6 J mice were fed with chow containing 0.2% cup for 4 weeks to induce oligodendrocytes (OLGs) depletion predominantly in the corpus callosum (CC). EA was administered at different doses (40 or 80 mg/kg body weight/day/i.p.) from the first day of cup diet. Oligodendrocytes apoptosis [TUNEL assay and myelin oligodendrocyte glycoprotein (MOG )/caspase-3 cells), gliosis (H&E staining, glial fibrillary acidic protein (GFAP ) and macrophage-3 (Mac-3 ) cells) and inflammatory markers (interleukin 17 (IL-17), interleukin 11 (IL-11) and stromal cell-derived factor 1 α (SDF-1α) or CXCL12] during cup intoxication were examined. RESULTS: High dose of EA (EA-80) increased mature oligodendrocytes population (MOG cells, p < 0.001), and decreased apoptosis (p < 0.05) compared with the cup mice. Treatment with both EA doses did not show any considerable effects on the expression of CXCL12, but significantly down-regulated the expression of IL-17 and up-regulated the expression of IL-11 in mRNA levels compared with the cup mice. Only treatment with EA-80 significantly decreased the population of active macrophage (MAC-3 cells, p < 0.001) but not reactive astrocytes (GFAP cells) compared with the cup mice. DISCUSSION AND CONCLUSION: In this model, EA-80 effectively reduces lesions via reduction of neuroinflammation and toxic effects of cup on mature OLGs. EA is a suitable therapeutic agent for moderate brain damage in neurodegenerative diseases such as multiple sclerosis.
[Mh] Termos MeSH primário: Cuprizona/toxicidade
Doenças Desmielinizantes/prevenção & controle
Ácido Elágico/farmacologia
Fármacos Neuroprotetores/farmacologia
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Astrócitos/efeitos dos fármacos
Astrócitos/metabolismo
Quimiocina CXCL12/metabolismo
Corpo Caloso/efeitos dos fármacos
Corpo Caloso/metabolismo
Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Regulação para Baixo/efeitos dos fármacos
Ácido Elágico/administração & dosagem
Marcação In Situ das Extremidades Cortadas
Interleucina-11/metabolismo
Interleucina-17/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Fármacos Neuroprotetores/administração & dosagem
Oligodendroglia/efeitos dos fármacos
Oligodendroglia/metabolismo
RNA Mensageiro/metabolismo
Regulação para Cima/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chemokine CXCL12); 0 (Interleukin-11); 0 (Interleukin-17); 0 (Neuroprotective Agents); 0 (RNA, Messenger); 19YRN3ZS9P (Ellagic Acid); 5N16U7E0AO (Cuprizone)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1080/13880209.2017.1319867


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[PMID]:28404595
[Au] Autor:Freeman L; Guo H; David CN; Brickey WJ; Jha S; Ting JP
[Ad] Endereço:Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
[Ti] Título:NLR members NLRC4 and NLRP3 mediate sterile inflammasome activation in microglia and astrocytes.
[So] Source:J Exp Med;214(5):1351-1370, 2017 May 01.
[Is] ISSN:1540-9538
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Inflammation in the brain accompanies several high-impact neurological diseases including multiple sclerosis (MS), stroke, and Alzheimer's disease. Neuroinflammation is sterile, as damage-associated molecular patterns rather than microbial pathogens elicit the response. The inflammasome, which leads to caspase-1 activation, is implicated in neuroinflammation. In this study, we reveal that lysophosphatidylcholine (LPC), a molecule associated with neurodegeneration and demyelination, elicits NLRP3 and NLRC4 inflammasome activation in microglia and astrocytes, which are central players in neuroinflammation. LPC-activated inflammasome also requires ASC (apoptotic speck containing protein with a CARD), caspase-1, cathepsin-mediated degradation, calcium mobilization, and potassium efflux but not caspase-11. To study the physiological relevance, and mice are studied in the cuprizone model of neuroinflammation and demyelination. Mice lacking both genes show the most pronounced reduction in astrogliosis and microglial accumulation accompanied by decreased expression of the LPC receptor G2A, whereas MS patient samples show increased G2A. These results reveal that NLRC4 and NLRP3, which normally form distinct inflammasomes, activate an LPC-induced inflammasome and are important in astrogliosis and microgliosis.
[Mh] Termos MeSH primário: Proteínas Reguladoras de Apoptose/fisiologia
Astrócitos/fisiologia
Proteínas de Ligação ao Cálcio/fisiologia
Inflamassomos/fisiologia
Microglia/fisiologia
Proteína 3 que Contém Domínio de Pirina da Família NLR/fisiologia
[Mh] Termos MeSH secundário: Animais
Astrócitos/efeitos dos fármacos
Astrócitos/patologia
Cuprizona/farmacologia
Modelos Animais de Doenças
Inflamação/patologia
Inflamação/fisiopatologia
Lisofosfatidilcolinas/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Microglia/efeitos dos fármacos
Microglia/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Apoptosis Regulatory Proteins); 0 (Calcium-Binding Proteins); 0 (Inflammasomes); 0 (Ipaf protein, mouse); 0 (Lysophosphatidylcholines); 0 (NLR Family, Pyrin Domain-Containing 3 Protein); 0 (Nlrp3 protein, mouse); 5N16U7E0AO (Cuprizone)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170414
[St] Status:MEDLINE
[do] DOI:10.1084/jem.20150237


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[PMID]:28238065
[Au] Autor:Hochstrasser T; Exner GL; Nyamoya S; Schmitz C; Kipp M
[Ad] Endereço:Department of Neuroanatomy, Ludwig-Maximilians-University of Munich, Pettenkoferstr. 11, 80336, Munich, Germany. tanja.hochstrasser@med.uni-muenchen.de.
[Ti] Título:Cuprizone-Containing Pellets Are Less Potent to Induce Consistent Demyelination in the Corpus Callosum of C57BL/6 Mice.
[So] Source:J Mol Neurosci;61(4):617-624, 2017 Apr.
[Is] ISSN:1559-1166
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo: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 0.25% cuprizone mixed into ground rodent chow does induce demyelination to a similar extent compared to a cuprizone-pellet intoxication protocol. We found that feeding of 0.25% cuprizone in ground chow provides a strong, well-defined, and reproducible demyelination along with increased accumulation of microglia and axonal damage in the corpus callosum, whereas all analyzed parameters were significantly less distinct in mice fed with cuprizone-containing pellets at an equivalent concentration of cuprizone at week 5. Even a higher concentration of cuprizone in pellet formulation was less potent compared to do so. This study illustrates that the established protocol of cuprizone intoxication (i.e., mixed in ground rodent chow) is the gold standard method to achieve consistent and reproducible demyelination. Why cuprizone loses its effectiveness in pellet formulation needs to be addressed in subsequent studies.
[Mh] Termos MeSH primário: Corpo Caloso/efeitos dos fármacos
Cuprizona/administração & dosagem
Doenças Desmielinizantes/etiologia
[Mh] Termos MeSH secundário: Administração Oral
Animais
Corpo Caloso/patologia
Cuprizona/toxicidade
Doenças Desmielinizantes/patologia
Modelos Animais de Doenças
Implantes de Medicamento/efeitos adversos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drug Implants); 5N16U7E0AO (Cuprizone)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170227
[St] Status:MEDLINE
[do] DOI:10.1007/s12031-017-0903-3


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[PMID]:28237816
[Au] Autor:Zhang J; Zhang ZG; Lu M; Wang X; Shang X; Elias SB; Chopp M
[Ad] Endereço:Department of Neurology, Henry Ford Health System, Detroit, MI 48202, United States. Electronic address: jingz@neuro.hfh.edu.
[Ti] Título:MiR-146a promotes remyelination in a cuprizone model of demyelinating injury.
[So] Source:Neuroscience;348:252-263, 2017 Apr 21.
[Is] ISSN:1873-7544
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo: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 5weeks. After termination of CPZ diet, the mice were randomly treated with continuous infusion of miR-146a mimics or mimic controls into the corpus callosum for 7days. Compared to the mimic control, infusion of miR-146a mimics facilitated remyelination assessed by increased myelin basic proteins in the corpus callosum, which was associated with augmentation of newly generated mature OLs. Infusion of miR-146a mimics also substantially elevated miR-146a levels in the corpus callosum and fluorescently tagged miR-146a mimics were mainly detected in OPCs. Western blot and double immmunofluorescent staining analysis showed that the miR-146a treatment considerably reduced IRAK1 protein levels and the number of IRAK1-positive cells, respectively. Collectively, these data indicate that exogenous miR-146a enhances remyelination, possibly by promoting OPCs to differentiate into myelinated OLs via targeting IRAK1.
[Mh] Termos MeSH primário: Corpo Caloso/efeitos dos fármacos
Doenças Desmielinizantes/tratamento farmacológico
MicroRNAs/uso terapêutico
Neurogênese/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Corpo Caloso/metabolismo
Cuprizona
Doenças Desmielinizantes/induzido quimicamente
Doenças Desmielinizantes/metabolismo
Camundongos
Camundongos Endogâmicos C57BL
MicroRNAs/farmacologia
Oligodendroglia/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MicroRNAs); 0 (Mirn146 microRNA, mouse); 5N16U7E0AO (Cuprizone)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170227
[St] Status:MEDLINE


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[PMID]:28235052
[Au] Autor:Komegae EN; Souza TA; Grund LZ; Lima C; Lopes-Ferreira M
[Ad] Endereço:Immunoregulation Unit, Special Laboratory of Applied Toxinology, Butantan Institute, São Paulo, Brazil.
[Ti] Título:Multiple functional therapeutic effects of TnP: A small stable synthetic peptide derived from fish venom in a mouse model of multiple sclerosis.
[So] Source:PLoS One;12(2):e0171796, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The pathological condition of multiple sclerosis (MS) relies on innate and adaptive immunity. New types of agents that beneficially modify the course of MS, stopping the progression and repairing the damage appear promising. Here, we studied TnP, a small stable synthetic peptide derived from fish venom in the control of inflammation and demyelination in experimental autoimmune encephalomyelitis as prophylactic treatment. TnP decreased the number of the perivascular infiltrates in spinal cord, and the activity of MMP-9 by F4/80+ macrophages were decreased after different regimen treatments. TnP reduces in the central nervous system the infiltration of IFN-γ-producing Th1 and IL-17A-producing Th17 cells. Also, treatment with therapeutic TnP promotes the emergence of functional Treg in the central nervous system entirely dependent on IL-10. Therapeutic TnP treatment accelerates the remyelination process in a cuprizone model of demyelination. These findings support the beneficial effects of TnP and provides a new therapeutic opportunity for the treatment of MS.
[Mh] Termos MeSH primário: Encefalomielite Autoimune Experimental/tratamento farmacológico
Venenos de Peixe/química
Fatores Imunológicos/farmacologia
Peptídeos/farmacologia
Medula Espinal/efeitos dos fármacos
Linfócitos T Reguladores/efeitos dos fármacos
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Antígenos de Diferenciação/genética
Antígenos de Diferenciação/imunologia
Brasil
Cuprizona
Modelos Animais de Doenças
Encefalomielite Autoimune Experimental/induzido quimicamente
Encefalomielite Autoimune Experimental/imunologia
Encefalomielite Autoimune Experimental/patologia
Feminino
Regulação da Expressão Gênica
Fatores Imunológicos/isolamento & purificação
Interferon gama/genética
Interferon gama/imunologia
Interleucina-10/genética
Interleucina-10/imunologia
Interleucina-17/genética
Interleucina-17/imunologia
Macrófagos/efeitos dos fármacos
Macrófagos/imunologia
Macrófagos/patologia
Metaloproteinase 9 da Matriz/genética
Metaloproteinase 9 da Matriz/imunologia
Camundongos
Esclerose Múltipla/tratamento farmacológico
Esclerose Múltipla/imunologia
Esclerose Múltipla/patologia
Peptídeos/isolamento & purificação
Perciformes/metabolismo
Medula Espinal/imunologia
Medula Espinal/patologia
Linfócitos T Reguladores/imunologia
Linfócitos T Reguladores/patologia
Células Th1/efeitos dos fármacos
Células Th1/imunologia
Células Th1/patologia
Células Th17/efeitos dos fármacos
Células Th17/imunologia
Células Th17/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Differentiation); 0 (Fish Venoms); 0 (Immunologic Factors); 0 (Interleukin-17); 0 (Peptides); 0 (monocyte-macrophage differentiation antigen); 130068-27-8 (Interleukin-10); 5N16U7E0AO (Cuprizone); 82115-62-6 (Interferon-gamma); EC 3.4.24.35 (Matrix Metalloproteinase 9)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170225
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0171796



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