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  1 / 15659 MEDLINE  
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[PMID]:28471051
[Au] Autor:Döring C; Regen T; Gertig U; van Rossum D; Winkler A; Saiepour N; Brück W; Hanisch UK; Janova H
[Ad] Endereço:Institute of Neuropathology, University Medical Center Göttingen, Göttingen, 37075, Germany.
[Ti] Título:A presumed antagonistic LPS identifies distinct functional organization of TLR4 in mouse microglia.
[So] Source:Glia;65(7):1176-1185, 2017 Jul.
[Is] ISSN:1098-1136
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Microglia as principle innate immune cells of the central nervous system (CNS) are the first line of defense against invading pathogens. They are capable of sensing infections through diverse receptors, such as Toll-like receptor 4 (TLR4). This receptor is best known for its ability to recognize bacterial lipopolysaccharide (LPS), a causative agent of gram-negative sepsis and septic shock. A putative, naturally occurring antagonist of TLR4 derives from the photosynthetic bacterium Rhodobacter sphaeroides. However, the antagonistic potential of R. sphaeroides LPS (Rs-LPS) is no universal feature, since several studies suggested agonistic rather than antagonistic actions of this molecule depending on the investigated mammalian species. Here we show the agonistic versus antagonistic potential of Rs-LPS in primary mouse microglia. We demonstrate that Rs-LPS efficiently induces the release of cytokines and chemokines, which depends on TLR4, MyD88, and TRIF, but not CD14. Furthermore, Rs-LPS is able to regulate the phagocytic capacity of microglia as agonist, while it antagonizes Re-LPS-induced MHC I expression. Finally, to our knowledge, we are the first to provide in vivo evidence for an agonistic potential of Rs-LPS, as it efficiently triggers the recruitment of peripheral immune cells to the endotoxin-challenged CNS. Together, our results argue for a versatile and complex organization of the microglial TLR4 system, which specifically translates exogenous signals into cellular functions. Importantly, as demonstrated here for microglia, the antagonistic potential of Rs-LPS needs to be considered with caution, as reactions to Rs-LPS not only differ by cell type, but even by function within one cell type.
[Mh] Termos MeSH primário: Lipopolissacarídeos/farmacologia
Microglia/efeitos dos fármacos
Receptor 4 Toll-Like/antagonistas & inibidores
Receptor 4 Toll-Like/metabolismo
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transporte Vesicular/genética
Proteínas Adaptadoras de Transporte Vesicular/metabolismo
Animais
Animais Recém-Nascidos
Encéfalo/citologia
Células Cultivadas
Corpo Estriado/efeitos dos fármacos
Citocinas/metabolismo
Relação Dose-Resposta a Droga
Receptores de Lipopolissacarídeos/genética
Receptores de Lipopolissacarídeos/metabolismo
Macrófagos/efeitos dos fármacos
Macrófagos/fisiologia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Bainha de Mielina/efeitos dos fármacos
Bainha de Mielina/patologia
Fator 88 de Diferenciação Mieloide/genética
Fator 88 de Diferenciação Mieloide/metabolismo
Fagocitose/efeitos dos fármacos
Fagocitose/fisiologia
Receptor 4 Toll-Like/genética
Regulação para Cima/efeitos dos fármacos
Regulação para Cima/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Vesicular Transport); 0 (Cytokines); 0 (Lipopolysaccharide Receptors); 0 (Lipopolysaccharides); 0 (Myeloid Differentiation Factor 88); 0 (TICAM-1 protein, mouse); 0 (Tlr4 protein, mouse); 0 (Toll-Like Receptor 4)
[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:170505
[St] Status:MEDLINE
[do] DOI:10.1002/glia.23151


  2 / 15659 MEDLINE  
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[PMID]:28743796
[Au] Autor:Roberts SL; Dun XP; Doddrell RDS; Mindos T; Drake LK; Onaitis MW; Florio F; Quattrini A; Lloyd AC; D'Antonio M; Parkinson DB
[Ad] Endereço:Plymouth University Peninsula Schools of Medicine and Dentistry, John Bull Building, Plymouth Science Park, Plymouth PL6 8BU, UK.
[Ti] Título:Sox2 expression in Schwann cells inhibits myelination and induces influx of macrophages to the nerve.
[So] Source:Development;144(17):3114-3125, 2017 09 01.
[Is] ISSN:1477-9129
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Correct myelination is crucial for the function of the peripheral nervous system. Both positive and negative regulators within the axon and Schwann cell function to ensure the correct onset and progression of myelination during both development and following peripheral nerve injury and repair. The Sox2 transcription factor is well known for its roles in the development and maintenance of progenitor and stem cell populations, but has also been proposed as a negative regulator of myelination in Schwann cells. We wished to test fully whether Sox2 regulates myelination and show here that, in mice, sustained Sox2 expression blocks myelination in the peripheral nerves and maintains Schwann cells in a proliferative non-differentiated state, which is also associated with increased inflammation within the nerve. The plasticity of Schwann cells allows them to re-myelinate regenerated axons following injury and we show that re-myelination is also blocked by Sox2 expression in Schwann cells. These findings identify Sox2 as a physiological regulator of Schwann cell myelination and its potential to play a role in disorders of myelination in the peripheral nervous system.
[Mh] Termos MeSH primário: Macrófagos/metabolismo
Bainha de Mielina/metabolismo
Nervos Periféricos/metabolismo
Fatores de Transcrição SOXB1/metabolismo
Células de Schwann/metabolismo
[Mh] Termos MeSH secundário: Animais
Biomarcadores/metabolismo
Caderinas/metabolismo
Proliferação Celular
Proteína 2 de Resposta de Crescimento Precoce/metabolismo
Proteínas de Fluorescência Verde/metabolismo
Camundongos Transgênicos
Atividade Motora
Condução Nervosa
Traumatismos dos Nervos Periféricos/metabolismo
Traumatismos dos Nervos Periféricos/patologia
Nervos Periféricos/patologia
Nervos Periféricos/ultraestrutura
Proteínas Proto-Oncogênicas c-jun/metabolismo
Ratos
Recuperação de Função Fisiológica
Células de Schwann/patologia
Transgenes
beta Catenina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers); 0 (Cadherins); 0 (Early Growth Response Protein 2); 0 (Proto-Oncogene Proteins c-jun); 0 (SOXB1 Transcription Factors); 0 (beta Catenin); 147336-22-9 (Green Fluorescent Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1242/dev.150656


  3 / 15659 MEDLINE  
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[PMID]:28467360
[Au] Autor:Herzfeld E; Speh L; Strauss C; Scheller C
[Ad] Endereço:Department of Neurosurgery, Martin-Luther University of Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany. eva.herzfeld@uk-halle.de.
[Ti] Título:Nimodipine but Not Nifedipine Promotes Expression of Fatty Acid 2-Hydroxylase in a Surgical Stress Model Based on Neuro2a Cells.
[So] Source:Int J Mol Sci;18(5), 2017 May 03.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Nimodipine is well characterized for the management of aneurysmal subarachnoid hemorrhage and has been shown to promote a better outcome and less delayed ischemic neurological deficits. Animal and clinical trials show neuroprotective efficacy following nerve injuries. We showed a neuroprotective effect on Neuro2a cells. Subsequent microarray analysis revealed-among others-fatty acid 2-hydroxylase (FA2H) upregulated by nimodipine in vitro, which is a component of myelin synthesis. Differentiated Neuro2a cells were analyzed for nimodipine-mediated survival considering stress treatment in comparison to nifedipine-treatment. Cell survival was determined by measurement of LDH activity in the culture medium. Nimodipine decreased surgery-like stress-induced cell death of differentiated Neuro2a cells. Neuro2a cell culture was analyzed for changes in FA2H expression induced by nimodipine or nifedipine in surgery-like stress conditions. We analyzed expression levels of FA2H mRNA and protein by qPCR using specific primers or a FA2H-specific antibody in nimodipine or nifedipine non- and pre-treated Neuro2a cell culture, respectively. Nimodipine but not nifedipine increases FA2H protein levels and also significantly increases mRNA levels of FA2H in both undifferentiated and differentiated Neuro2a cells. Our findings indicate that higher expression of FA2H induced by nimodipine may cause higher survival of Neuro2a cells stressed with surgery-like stressors.
[Mh] Termos MeSH primário: Bloqueadores dos Canais de Cálcio/farmacologia
Resposta ao Choque Térmico/efeitos dos fármacos
Oxigenases de Função Mista/metabolismo
Fármacos Neuroprotetores/farmacologia
Procedimentos Neurocirúrgicos/efeitos adversos
Nifedipino/farmacologia
Nimodipino/farmacologia
Estresse Oxidativo/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Morte Celular/efeitos dos fármacos
Diferenciação Celular/efeitos dos fármacos
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Expressão Gênica
Camundongos
Oxigenases de Função Mista/genética
Bainha de Mielina/metabolismo
Nimodipino/uso terapêutico
RNA Mensageiro/genética
Estresse Mecânico
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channel Blockers); 0 (Neuroprotective Agents); 0 (RNA, Messenger); 57WA9QZ5WH (Nimodipine); EC 1.- (Mixed Function Oxygenases); EC 1.- (fatty acid alpha-hydroxylase); I9ZF7L6G2L (Nifedipine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE


  4 / 15659 MEDLINE  
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[PMID]:29329312
[Au] Autor:Scurfield A; Latimer DC
[Ad] Endereço:Department of Physics, University of Puget Sound, Tacoma, Washington, United States of America.
[Ti] Título:A computational study of the impact of inhomogeneous internodal lengths on conduction velocity in myelinated neurons.
[So] Source:PLoS One;13(1):e0191106, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Age-related decreases in the conduction velocity (CV) of action potentials along myelinated axons have been linked to morphological changes in the myelin sheath. In particular, evidence suggests the presence of segmental demyelination and remyelination of axons. In remyelinated segments, the distance between adjacent nodes of Ranvier is typically shorter, and myelin sheaths are thinner. Both experimental and computational evidence indicates that shortened internodes slows CV. In this computational study, we determine the impact of progressive segmental demyelination and remyelination, modeled by shorter internodes with thinner myelin sheaths interspersed with normal ones, upon the CV. We find that CV progressively decreases as the number of remyelinated segments increases, but this decrease is greater than one would expect from an estimate of the CV based merely upon the number of short and long internodes. We trace the additional suppression of the CV to transitions between long and short internodes. Our study presents an important consideration for the precise modeling of neural circuits with remyelinated neurons.
[Mh] Termos MeSH primário: Biologia Computacional
Bainha de Mielina/metabolismo
Neurônios/metabolismo
[Mh] Termos MeSH secundário: Potenciais de Ação
Animais
Neurônios/fisiologia
Nós Neurofibrosos/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191106


  5 / 15659 MEDLINE  
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[PMID]:29293550
[Au] Autor:Lévy S; Guertin MC; Khatibi A; Mezer A; Martinu K; Chen JI; Stikov N; Rainville P; Cohen-Adad J
[Ad] Endereço:NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada.
[Ti] Título:Test-retest reliability of myelin imaging in the human spinal cord: Measurement errors versus region- and aging-induced variations.
[So] Source:PLoS One;13(1):e0189944, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To implement a statistical framework for assessing the precision of several quantitative MRI metrics sensitive to myelin in the human spinal cord: T1, Magnetization Transfer Ratio (MTR), saturation imposed by an off-resonance pulse (MTsat) and Macromolecular Tissue Volume (MTV). METHODS: Thirty-three healthy subjects within two age groups (young, elderly) were scanned at 3T. Among them, 16 underwent the protocol twice to assess repeatability. Statistical reliability indexes such as the Minimal Detectable Change (MDC) were compared across metrics quantified within different cervical levels and white matter (WM) sub-regions. The differences between pathways and age groups were quantified and interpreted in context of the test-retest repeatability of the measurements. RESULTS: The MDC was respectively 105.7ms, 2.77%, 0.37% and 4.08% for T1, MTR, MTsat and MTV when quantified over all WM, while the standard-deviation across subjects was 70.5ms, 1.34%, 0.20% and 2.44%. Even though particular WM regions did exhibit significant differences, these differences were on the same order as test-retest errors. No significant difference was found between age groups for all metrics. CONCLUSION: While T1-based metrics (T1 and MTV) exhibited better reliability than MT-based measurements (MTR and MTsat), the observed differences between subjects or WM regions were comparable to (and often smaller than) the MDC. This makes it difficult to determine if observed changes are due to variations in myelin content, or simply due to measurement error. Measurement error remains a challenge in spinal cord myelin imaging, but this study provides statistical guidelines to standardize the field and make it possible to conduct large-scale multi-center studies.
[Mh] Termos MeSH primário: Envelhecimento/metabolismo
Bainha de Mielina/metabolismo
Medula Espinal/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Feminino
Seres Humanos
Masculino
Meia-Idade
Reprodutibilidade dos Testes
Medula Espinal/diagnóstico por imagem
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180103
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189944


  6 / 15659 MEDLINE  
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[PMID]:27776262
[Au] Autor:Sterling NW; Du G; Lewis MM; Swavely S; Kong L; Styner M; Huang X
[Ad] Endereço:Department of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA, USA.
[Ti] Título:Cortical gray and subcortical white matter associations in Parkinson's disease.
[So] Source:Neurobiol Aging;49:100-108, 2017 Jan.
[Is] ISSN:1558-1497
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cortical atrophy has been documented in both Parkinson's disease (PD) and healthy aging, but its relationship to changes in subcortical white matter is unknown. This was investigated by obtaining T1- and diffusion-weighted images from 76 PD and 70 controls at baseline and 18 and 36 months, from which cortical volumes and underlying subcortical white matter axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) were determined. Twelve of 69 cortical subregions had significant group differences, and for these, underlying subcortical white matter was explored. At baseline, higher cortical volumes were significantly correlated with lower underlying subcortical white matter AD, RD, and higher FA (ps ≤ 0.017) in PD. Longitudinally, higher rates of cortical atrophy in PD were associated with increased rates of change in AD RD, and FA values (ps ≤ 0.0013) in 2 subregions explored. The significant gray-white matter associations were not found in controls. Thus, unlike healthy aging, cortical atrophy and subcortical white matter changes may not be independent events in PD.
[Mh] Termos MeSH primário: Córtex Cerebral/patologia
Substância Cinzenta/patologia
Doença de Parkinson/patologia
Substância Branca/patologia
[Mh] Termos MeSH secundário: Idoso
Anisotropia
Atrofia
Córtex Cerebral/diagnóstico por imagem
Imagem de Difusão por Ressonância Magnética
Imagem de Tensor de Difusão
Feminino
Substância Cinzenta/diagnóstico por imagem
Seres Humanos
Masculino
Meia-Idade
Bainha de Mielina
Neuroimagem
Doença de Parkinson/diagnóstico por imagem
Substância Branca/diagnóstico por imagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180112
[Lr] Data última revisão:
180112
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


  7 / 15659 MEDLINE  
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[PMID]:28452990
[Au] Autor:Pircher A; Montali M; Berberat J; Remonda L; Killer HE
[Ad] Endereço:Department of Ophthalmology, Cantonal Hospital Aarau, Aarau, Switzerland.
[Ti] Título:Relationship between the optic nerve sheath diameter and lumbar cerebrospinal fluid pressure in patients with normal tension glaucoma.
[So] Source:Eye (Lond);31(9):1365-1372, 2017 Sep.
[Is] ISSN:1476-5454
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PurposeTo investigate on the relationship between the optic nerve sheath diameter (ONSD) and the lumbar cerebrospinal fluid pressure (CSF-p) in Caucasian patients with normal tension glaucoma (NTG).Patients and methodsRetrospective analysis of medical records of patients with open-angle glaucoma in the period from 2005 to 2015 from the Ophthalmology Department, Cantonal Hospital Aarau, Switzerland was performed. A total of 38 patients (mean age 68.6±11.3 years, 21 females and 17 males) fulfilled the diagnostic criteria of NTG and underwent computed tomography (CT) of the orbit and lumbar puncture (LP). In total, 38 age- and gender-matched Caucasian subjects (mean age: 68.9±10.9 years) without known ON diseases served as controls for ONSD measurements. ONSDs were measured at a distance of 3 mm from the posterior globe and lumbar CSF-p was related to the measurements. Statistical analysis was performed by using the independent two-tailed t-test and the non-parametric Spearman's correlation test.ResultsThe mean ONSD in NTGs measured 6.4±0.9 mm and in controls 5.4±0.6 mm. The difference between NTGs and controls showed statistical significance (t-test: P<0.000). The mean CSF-p in NTG was 11.6±3.7 mm Hg. There was no statistical significant correlation between ONSD and CSF-p (Spearman's correlation coefficient ρ=0.06, P=0.72).ConclusionsThis study demonstrates enlarged ONSDs and normal lumbar CSF-p in 38 Caucasian NTG patients. As enlarged ONSDs generally are associated with increased intracranial CSF-p, these results can be explained by a disturbed communication of CSF-p between the intracranial and intraorbital subarachnoid spaces.
[Mh] Termos MeSH primário: Pressão do Líquido Cefalorraquidiano/fisiologia
Glaucoma de Baixa Tensão/fisiopatologia
Bainha de Mielina/patologia
Nervo Óptico/patologia
[Mh] Termos MeSH secundário: Idoso
Grupo com Ancestrais do Continente Europeu
Feminino
Seres Humanos
Pressão Intraocular/fisiologia
Masculino
Nervo Óptico/diagnóstico por imagem
Estudos Retrospectivos
Punção Espinal
Espaço Subaracnóideo
Tomografia Computadorizada por Raios X
Tonometria Ocular
Testes de Campo Visual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180109
[Lr] Data última revisão:
180109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1038/eye.2017.70


  8 / 15659 MEDLINE  
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[PMID]:29253893
[Au] Autor:Chen Y; Zhen W; Guo T; Zhao Y; Liu A; Rubio JP; Krull D; Richardson JC; Lu H; Wang R
[Ad] Endereço:Neuro-immunology Discovery Performance Unit, GSK, Shanghai, China.
[Ti] Título:Histamine Receptor 3 negatively regulates oligodendrocyte differentiation and remyelination.
[So] Source:PLoS One;12(12):e0189380, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Agents promoting oligodendrocyte precursor cell differentiation have the potential to restore halted and/or delayed remyelination in patients with multiple sclerosis. However, few therapeutic targets have been identified. The objective of this study was to identify novel targets for promotion of remyelination and characterize their activity in vitro and in vivo. METHODS: A high-content screening assay with differentiation of primary rat oligodendrocyte precursor cells was used to screen GSK-proprietary annotated libraries for remyelination-promoting compounds. Compounds were further validated in vitro and in vivo models; clinical relevance of target was confirmed in human post-mortem brain sections from patients with MS. RESULTS: Of ~1000 compounds screened, 36 promoted oligodendrocyte precursor cell differentiation in a concentration-dependent manner; seven were histamine receptor-3 (H3R) antagonists. Inverse agonists of H3R but not neutral antagonists promoted oligodendrocyte precursor cell (OPC) differentiation. H3R was expressed throughout OPC differentiation; H3R expression was transiently upregulated on Days 3-5 and subsequently downregulated. H3R gene knockdown in OPCs increased the expression of differentiation markers and the number of mature oligodendrocytes. Overexpression of full-length H3R reduced differentiation marker expression and the number of mature cells. H3R inverse agonist GSK247246 reduced intracellular cyclic AMP (cAMP) and downstream cAMP response element-binding protein (CREB) phosphorylation in a dose-dependent manner. Histone deacetylase (HDAC-1) and Hes-5 were identified as key downstream targets of H3R during OPC differentiation. In the mouse cuprizone/rapamycin model of demyelination, systemic administration of brain-penetrable GSK247246 enhanced remyelination and subsequently protected axons. Finally, we detected high H3R expression in oligodendroglial cells from demyelination lesions in human samples of patients with MS, and validated a genetic association between an exonic single nucleotide polymorphism in HRH3 and susceptibility to multiple sclerosis. CONCLUSIONS: From phenotypic screening to human genetics, we provide evidence for H3R as a novel therapeutic target to promote remyelination in patients with multiple sclerosis.
[Mh] Termos MeSH primário: Esclerose Múltipla/genética
Bainha de Mielina/metabolismo
Oligodendroglia/citologia
Receptores Histamínicos H3/metabolismo
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Encéfalo/patologia
Diferenciação Celular
Proliferação Celular
Glutationa Transferase/metabolismo
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Esclerose Múltipla/tratamento farmacológico
Esclerose Múltipla/metabolismo
Oligodendroglia/metabolismo
Fenótipo
Polimorfismo de Nucleotídeo Único
Prosencéfalo/patologia
Ratos
Receptores Histamínicos H3/genética
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Histamine H3); EC 2.5.1.18 (Glutathione Transferase)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171219
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189380


  9 / 15659 MEDLINE  
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[PMID]:29216327
[Au] Autor:Kuboyama K; Tanga N; Suzuki R; Fujikawa A; Noda M
[Ad] Endereço:Division of Molecular Neurobiology, National Institute for Basic Biology (NIBB), Okazaki, Aichi, Japan.
[Ti] Título:Protamine neutralizes chondroitin sulfate proteoglycan-mediated inhibition of oligodendrocyte differentiation.
[So] Source:PLoS One;12(12):e0189164, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo: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. PRM also bound to the extracellular region of protein tyrosine phosphatase receptor type Z (PTPRZ), a membrane-spanning CSPG predominantly expressed in OPCs, and functioned as a ligand mimetic of PTPRZ, thereby suppressing its negative regulatory activity on oligodendrocyte differentiation. In primary cultures, the differentiation of OPCs from wild-type and Ptprz-deficient mice was equally enhanced by PRM. Moreover, the intranasal administration of PRM accelerated myelination in the developing mouse brain, and its intracerebroventricular administration stimulated remyelination after cuprizone-induced demyelination. These results indicate that PRM has CSPG-neutralizing activity which promotes oligodendrocyte differentiation under developmental and morbid conditions.
[Mh] Termos MeSH primário: Diferenciação Celular/efeitos dos fármacos
Proteoglicanas de Sulfatos de Condroitina/metabolismo
Oligodendroglia/citologia
Protaminas/farmacologia
[Mh] Termos MeSH secundário: Animais
Encéfalo/citologia
Encéfalo/efeitos dos fármacos
Camundongos
Bainha de Mielina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chondroitin Sulfate Proteoglycans); 0 (Protamines)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189164


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[PMID]:29176903
[Au] Autor:Chu TH; Cummins K; Sparling JS; Tsutsui S; Brideau C; Nilsson KPR; Joseph JT; Stys PK
[Ad] Endereço:Hotchkiss Brain Institute, Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
[Ti] Título:Axonal and myelinic pathology in 5xFAD Alzheimer's mouse spinal cord.
[So] Source:PLoS One;12(11):e0188218, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:As an extension of the brain, the spinal cord has unique properties which could allow us to gain a better understanding of CNS pathology. The brain and cord share the same cellular components, yet the latter is simpler in cytoarchitecture and connectivity. In Alzheimer's research, virtually all focus is on brain pathology, however it has been shown that transgenic Alzheimer's mouse models accumulate beta amyloid plaques in spinal cord, suggesting that the cord possesses the same molecular machinery and conditions for plaque formation. Here we report a spatial-temporal map of plaque load in 5xFAD mouse spinal cord. We found that plaques started to appear at 11 weeks, then exhibited a time dependent increase and differential distribution along the cord. More plaques were found in cervical than other spinal levels at all time points examined. Despite heavy plaque load at 6 months, the number of cervical motor neurons in 5xFAD mice is comparable to wild type littermates. On detailed microscopic examination, fine beta amyloid-containing and beta sheet-rich thread-like structures were found in the peri-axonal space of many axons. Importantly, these novel structures appear before any plaque deposits are visible in young mice spinal cord and they co-localize with axonal swellings at later stages, suggesting that these thread-like structures might represent the initial stages of plaque formation, and could play a role in axonal damage. Additionally, we were able to demonstrate increasing myelinopathy in aged 5xFAD mouse spinal cord using the lipid probe Nile Red with high resolution. Collectively, we found significant amyloid pathology in grey and white matter of the 5xFAD mouse spinal cord which indicates that this structure maybe a useful platform to study mechanisms of Alzheimer's pathology and disease progression.
[Mh] Termos MeSH primário: Doença de Alzheimer/patologia
Axônios/patologia
Bainha de Mielina/patologia
Medula Espinal/patologia
[Mh] Termos MeSH secundário: Envelhecimento
Precursor de Proteína beta-Amiloide/metabolismo
Animais
Substância Cinzenta/patologia
Seres Humanos
Camundongos Transgênicos
Neurônios Motores/patologia
Neuroglia/patologia
Placa Amiloide/patologia
Substância Branca/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Protein Precursor)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188218



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