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[PMID]:29353725
[Au] Autor:Haider A; Spinelli F; Herde AM; Mu B; Keller C; Margelisch M; Weber M; Schibli R; Mu L; Ametamey SM
[Ad] Endereço:Institute of Pharmaceutical Sciences, ETH Zürich, 8093 Zürich, Switzerland.
[Ti] Título:Evaluation of 4-oxo-quinoline-based CB2 PET radioligands in R6/2 chorea huntington mouse model and human ALS spinal cord tissue.
[So] Source:Eur J Med Chem;145:746-759, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:The cannabinoid receptor 2 (CB2) has been implicated in a series of neurodegenerative disorders and has emerged as an interesting biological target for therapeutic as well as diagnostic purposes. In the present work, we describe an improved radiosynthetic approach to obtain the previously reported CB2-specific PET radioligand [ F]RS-126 in higher radiochemical yields and molar activities. Additionally, the study revealed that prolongation of the [ F]RS-126 fluoroalkyl side chain ultimately leads to an improved stability towards mouse liver enzymes but is accompanied by a reduction in selectivity over the cannabinoid receptor 1 (CB1). Huntington-related phenotypic changes as well as striatal D2R downregulation were confirmed for the transgenic R6/2 mouse model. CB2 upregulation in R6/2 Chorea Huntington mice was observed in hippocampus, cortex, striatum and cerebellum by qPCR, however, these results could not be confirmed at the protein level by PET imaging. Furthermore, we evaluated the utility of the newly developed [ C]RS-028, a potent [ F]RS-126 derivative with increased polarity and high selectivity over CB1 in post-mortem human ALS spinal cord and control tissue. Applying in vitro autoradiography, the translational relevance of CB2 imaging was demonstrated by the specific binding of [ C]RS-028 to post-mortem human ALS spinal cord tissue.
[Mh] Termos MeSH primário: Esclerose Amiotrófica Lateral/diagnóstico por imagem
Doença de Huntington/diagnóstico por imagem
Quinolinas/química
Compostos Radiofarmacêuticos/química
Receptor CB2 de Canabinoide/metabolismo
Medula Espinal/diagnóstico por imagem
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Radioisótopos de Flúor
Seres Humanos
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Estrutura Molecular
Tomografia por Emissão de Pósitrons
Quinolinas/síntese química
Compostos Radiofarmacêuticos/síntese química
Ratos
Ratos Wistar
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fluorine Radioisotopes); 0 (Quinolines); 0 (Radiopharmaceuticals); 0 (Receptor, Cannabinoid, CB2); E66400VT9R (quinoline)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180123
[St] Status:MEDLINE


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[PMID]:29340519
[Au] Autor:Barboza LA; Ghisi NC
[Ad] Endereço:Laboratório de Biologia Molecular, Universidade Tecnológica Federal do Paraná, Dois Vizinhos, PR, Brasil.
[Ti] Título:Evaluating the current state of the art of Huntington disease research: a scientometric analysis.
[So] Source:Braz J Med Biol Res;51(3):e6299, 2018 Jan 11.
[Is] ISSN:1414-431X
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Huntington disease (HD) is an incurable neurodegenerative disorder caused by a dominant mutation on the 4th chromosome. We aim to present a scientometric analysis of the extant scientific undertakings devoted to better understanding HD. Therefore, a quantitative study was performed to examine the current state-of-the-art approaches that foster researchers' understandings of the current knowledge, research trends, and research gaps regarding this disorder. We performed literature searches of articles that were published up to September 2016 in the "ISI Web of Science™" (http://apps.webofknowledge.com/). The keyword used was "Huntington disease". Of the initial 14,036 articles that were obtained, 7732 were eligible for inclusion in the study according to their relevance. Data were classified according to language, country of publication, year, and area of concentration. The country leader regarding the number of studies published on HD is the United States, accounting for nearly 30% of all publications, followed by England and Germany, who have published 10 and 7% of all publications, respectively. Regarding the language in which the articles were written, 98% of publications were in English. The first publication to be found on HD was published in 1974. A surge of publications on HD can be seen from 1996 onward. In relation to the various knowledge areas that emerged, most publications were in the fields of neuroscience and neurology, likely because HD is a neurodegenerative disorder. Publications written in areas such as psychiatry, genetics, and molecular biology also predominated.
[Mh] Termos MeSH primário: Pesquisa Biomédica/estatística & dados numéricos
Doença de Huntington/genética
[Mh] Termos MeSH secundário: Brasil
Coreia/genética
Seres Humanos
Doença de Huntington/diagnóstico
Doença de Huntington/terapia
Internacionalidade
Linguagem
Complexo Mediador/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (MED12 protein, human); 0 (Mediator Complex)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE


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[PMID]:29324753
[Au] Autor:Langfelder P; Gao F; Wang N; Howland D; Kwak S; Vogt TF; Aaronson JS; Rosinski J; Coppola G; Horvath S; Yang XW
[Ad] Endereço:Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America.
[Ti] Título:MicroRNA signatures of endogenous Huntingtin CAG repeat expansion in mice.
[So] Source:PLoS One;13(1):e0190550, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In Huntington's disease (HD) patients and in model organisms, messenger RNA transcriptome has been extensively studied; in contrast, comparatively little is known about expression and potential role of microRNAs. Using RNA-sequencing, we have quantified microRNA expression in four brain regions and liver, at three different ages, from an allelic series of HD model mice with increasing CAG length in the endogenous Huntingtin gene. Our analyses reveal CAG length-dependent microRNA expression changes in brain, with 159 microRNAs selectively altered in striatum, 102 in cerebellum, 51 in hippocampus, and 45 in cortex. In contrast, a progressive CAG length-dependent microRNA dysregulation was not observed in liver. We further identify microRNAs whose transcriptomic response to CAG length expansion differs significantly among the brain regions and validate our findings in data from a second, independent cohort of mice. Using existing mRNA expression data from the same animals, we assess the possible relationships between microRNA and mRNA expression and highlight candidate microRNAs that are negatively correlated with, and whose predicted targets are enriched in, CAG-length dependent mRNA modules. Several of our top microRNAs (Mir212/Mir132, Mir218, Mir128 and others) have been previously associated with aspects of neuronal development and survival. This study provides an extensive resource for CAG length-dependent changes in microRNA expression in disease-vulnerable and -resistant brain regions in HD mice, and provides new insights for further investigation of microRNAs in HD pathogenesis and therapeutics.
[Mh] Termos MeSH primário: Proteína Huntingtina/genética
Doença de Huntington/genética
MicroRNAs/genética
Repetições de Trinucleotídeos
[Mh] Termos MeSH secundário: Animais
Encéfalo/metabolismo
Seres Humanos
Camundongos
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; VALIDATION STUDIES
[Nm] Nome de substância:
0 (HTT protein, human); 0 (Huntingtin Protein); 0 (MicroRNAs)
[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:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190550


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[PMID]:28453532
[Au] Autor:Sadeghi M; Barlow-Krelina E; Gibbons C; Shaikh KT; Fung WLA; Meschino WS; Till C
[Ad] Endereço:Department of Psychology, York University, Toronto, Ontario, Canada.
[Ti] Título:Feasibility of computerized working memory training in individuals with Huntington disease.
[So] Source:PLoS One;12(4):e0176429, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: Huntington disease (HD) is associated with a variety of cognitive deficits, with prominent difficulties in working memory (WM). WM deficits are notably compromised in early-onset and prodromal HD patients. This study aimed to determine the feasibility of a computerized WM training program (Cogmed QM), novel to the HD population. METHODS: Nine patients, aged 26-62, with early stage HD underwent a 25-session (5 days/week for 5 weeks) WM training program (Cogmed QM). Training exercises involved the manipulation and storage of verbal and visuospatial information, with difficulty adapted as a function of individual performance. Neuropsychological testing was conducted before and after training, and performance on criterion WM measures (Digit Span and Spatial Span), near-transfer WM measures (Symbol Span and Auditory WM), and control measures were evaluated. Post-training interviews about patient experience were thematically analyzed using NVivo software. RESULTS: Seven of nine patients demonstrated adherence to the training and completed all sessions within the recommended timeframe of 5 weeks. All adherent patients showed improvement on the Cogmed tasks as defined by the Improvement Index (M = 22.17, SD = 8.84, range = 13-36). All adherent patients reported that they found training helpful (n = 7), and almost all felt that their memory improved (n = 6). Participants also expressed that the training was difficult, sometimes frustrating, and time consuming. CONCLUSIONS: This pilot study provides support for feasibility of computerized WM training in early-stage patients with HD. Results suggest that HD patients perceive benefits of intensive WM training, though a full-scale and controlled intervention project is needed to understand the size of the effect and reliability of changes over time. TRIAL REGISTRATION: ClinicalTrials.gov, Registry number NCT02926820.
[Mh] Termos MeSH primário: Doença de Huntington/fisiopatologia
Doença de Huntington/terapia
Memória de Curto Prazo
[Mh] Termos MeSH secundário: Adulto
Estudos de Viabilidade
Feminino
Seres Humanos
Entrevistas como Assunto
Masculino
Meia-Idade
Testes Neuropsicológicos
Cooperação do Paciente
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180121
[Lr] Data última revisão:
180121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0176429


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[PMID]:29272284
[Au] Autor:Hensman Moss DJ; Robertson N; Farmer R; Scahill RI; Haider S; Tessari MA; Flynn G; Fischer DF; Wild EJ; Macdonald D; Tabrizi SJ
[Ad] Endereço:Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom.
[Ti] Título:Quantification of huntingtin protein species in Huntington's disease patient leukocytes using optimised electrochemiluminescence immunoassays.
[So] Source:PLoS One;12(12):e0189891, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative condition caused by an expanded CAG repeat in the gene encoding huntingtin (HTT). Optimizing peripheral quantification of huntingtin throughout the course of HD is valuable not only to illuminate the natural history and pathogenesis of disease, but also to detect peripheral effects of drugs in clinical trial. RATIONALE: We previously demonstrated that mutant HTT (mHTT) was significantly elevated in purified HD patient leukocytes compared with controls and that these levels track disease progression. Our present study investigates whether the same result can be achieved with a simpler and more scalable collection technique that is more suitable for clinical trials. METHODS: We collected whole blood at 133 patient visits in two sample sets and generated peripheral blood mononuclear cells (PBMCs). Levels of mHTT, as well as N-, and C-terminal and mid-region huntingtin were measured in the PBMCs using ELISA-based Meso Scale Discovery (MSD) electrochemiluminescence immunoassay platforms, and we evaluated the relationship between different HTT species, disease stage, and brain atrophy on magnetic resonance imaging. CONCLUSIONS: The assays were sensitive and accurate. We confirm our previous findings that mHTT increases with advancing disease stage in patient PBMCs, this time using a simple collection protocol and scalable assay.
[Mh] Termos MeSH primário: Ensaio de Imunoadsorção Enzimática/métodos
Proteína Huntingtina/sangue
Doença de Huntington/sangue
Leucócitos/metabolismo
[Mh] Termos MeSH secundário: Encéfalo/diagnóstico por imagem
Estudos Transversais
Eletroquímica
Seres Humanos
Proteína Huntingtina/genética
Doença de Huntington/diagnóstico por imagem
Luminescência
Mutação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (HTT protein, human); 0 (Huntingtin Protein)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171223
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189891


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[PMID]:29069396
[Au] Autor:Cisbani G; Maxan A; Kordower JH; Planel E; Freeman TB; Cicchetti F
[Ad] Endereço:Centre de Recherche du CHU de Québec-Université Laval, Axe Neurosciences, 2705 Boulevard Laurier, Québec, QC, Canada.
[Ti] Título:Presence of tau pathology within foetal neural allografts in patients with Huntington's and Parkinson's disease.
[So] Source:Brain;140(11):2982-2992, 2017 Nov 01.
[Is] ISSN:1460-2156
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cell replacement has been explored as a therapeutic strategy to repair the brain in patients with Huntington's and Parkinson's disease. Post-mortem evaluations of healthy grafted tissue in such cases have revealed the development of Huntington- or Parkinson-like pathology including mutant huntingtin aggregates and Lewy bodies. An outstanding question remains if tau pathology can also be seen in patients with Huntington's and Parkinson's disease who had received foetal neural allografts. This was addressed by immunohistochemical/immunofluorescent stainings performed on grafted tissue of two Huntington's disease patients, who came to autopsy 9 and 12 years post-transplantation, and two patients with Parkinson's disease who came to autopsy 18 months and 16 years post-transplantation. We show that grafts also contain tau pathology in both types of transplanted patients. In two patients with Huntington's disease, the grafted tissue showed the presence of hyperphosphorylated tau [both AT8 (phospho-tau Ser202 and Thr205) and CP13 (pSer202) immunohistochemical stainings] pathological inclusions, neurofibrillary tangles and neuropil threads. In patients with Parkinson's disease, the grafted tissue was characterized by hyperphosphorylated tau (AT8; immunofluorescent staining) pathological inclusions, neurofibrillary tangles and neuropil threads but only in the patient who came to autopsy 16 years post-transplantation. Abundant tau-related pathology was observed in the cortex and striatum of all cases studied. While the striatum of the grafted Huntington's disease patient revealed an equal amount of 3-repeat and 4-repeat isoforms of tau, the grafted tissue showed elevated 4-repeat isoforms by western blot. This suggests that transplants may have acquired tau pathology from the host brain, although another possibility is that this was due to acceleration of ageing. This finding not only adds to the recent reports that tau pathology is a feature of these neurodegenerative diseases, but also that tau pathology can manifest in healthy neural tissue transplanted into the brains of patients with two distinct neurodegenerative disorders.
[Mh] Termos MeSH primário: Aloenxertos/patologia
Transplante de Tecido Fetal
Doença de Huntington/patologia
Neostriado/transplante
Doença de Parkinson/patologia
Agregação Patológica de Proteínas/patologia
Proteínas tau/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Aloenxertos/metabolismo
Autopsia
Estudos de Casos e Controles
Criança
Feminino
Seres Humanos
Doença de Huntington/metabolismo
Doença de Huntington/terapia
Masculino
Meia-Idade
Neostriado/metabolismo
Neostriado/patologia
Doença de Parkinson/metabolismo
Doença de Parkinson/terapia
Agregação Patológica de Proteínas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MAPT protein, human); 0 (tau Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171026
[St] Status:MEDLINE
[do] DOI:10.1093/brain/awx255


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[PMID]:29016656
[Au] Autor:Schuldenzucker V; Schubert R; Muratori LM; Freisfeld F; Rieke L; Matheis T; Schramke S; Motlik J; Kemper N; Radespiel U; Reilmann R
[Ad] Endereço:George-Huntington-Institute, Technology-Park, Muenster, Germany.
[Ti] Título:Behavioral testing of minipigs transgenic for the Huntington gene-A three-year observational study.
[So] Source:PLoS One;12(10):e0185970, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Large animal models of Huntington's disease (HD) may increase the reliability of translating preclinical findings to humans. Long live expectancy offers opportunities particularly for disease modifying approaches, but also challenges. The transgenic (tg) HD minipig model assessed in this study exhibits a high genetic homology with humans, similar body weight, and comparable brain structures. To test long-term safety, tolerability, and efficacy of novel therapeutic approaches in this model reliable assessments applicable longitudinally for several years are warranted for all phenotypical domains relevant in HD. OBJECTIVE: To investigate whether the tests proposed assessing motor, cognitive and behavioral domains can be applied repetitively over a 3-year period in minipigs with acceptable variability or learning effects and whether tgHD minipigs reveal changes in these domains compared to wildtype (wt) minipigs suggesting the development of an HD phenotype. METHODS: A cohort of 14 tgHD and 18 wt minipigs was followed for three years. Tests applied every six months included a tongue coordination and hurdle test for the motor domain, a color discrimination test for cognition, and a dominance test for assessing behavior. Statistical analyses were performed using repeated ANOVA for longitudinal group comparisons and Wilcoxon-tests for intra-visit differences between tgHD and wt minipigs. RESULTS: All tests applied demonstrated feasibility, acceptable variance and good consistency during the three-year period. No significant differences between tgHD and wt minipigs were detected suggesting lack of a phenotype before the age of four years. CONCLUSIONS: The assessment battery presented offers measures in all domains relevant for HD and can be applied in long-term phenotyping studies with tgHD minipigs. The observation of this cohort should be continued to explore the timeline of phenotype development and provide information for future interventional studies.
[Mh] Termos MeSH primário: Comportamento Animal/fisiologia
Doença de Huntington/fisiopatologia
Porco Miniatura/fisiologia
Suínos/fisiologia
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Feminino
Seres Humanos
Proteína Huntingtina/genética
Proteína Huntingtina/fisiologia
Aprendizagem/fisiologia
Língua/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Huntingtin Protein)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171011
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185970


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[PMID]:28938121
[Au] Autor:Guedes-Dias P; Holzbaur ELF
[Ad] Endereço:Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6085, USA.
[Ti] Título:Huntingtin Fibrils Poke Membranes.
[So] Source:Cell;171(1):32-33, 2017 09 21.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A hallmark of Huntington's disease is the presence of intracellular aggregates of mutant huntingtin, the pathological significance of which has long been debated. Using cryo-electron tomography, Bauerlein et al. reveal the fibrillary structure of huntingtin aggregates in situ and show that huntingtin fibrils interact with the endoplasmic reticulum, distorting its morphology and dynamics.
[Mh] Termos MeSH primário: Proteína Huntingtina
Proteínas do Tecido Nervoso/química
[Mh] Termos MeSH secundário: Animais
Retículo Endoplasmático
Seres Humanos
Doença de Huntington
Proteínas Nucleares/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; COMMENT
[Nm] Nome de substância:
0 (Huntingtin Protein); 0 (Nerve Tissue Proteins); 0 (Nuclear Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170923
[St] Status:MEDLINE


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[PMID]:28934250
[Au] Autor:Cabanas M; Bassil F; Mons N; Garret M; Cho YH
[Ad] Endereço:Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS UMR 5287, Pessac, France.
[Ti] Título:Changes in striatal activity and functional connectivity in a mouse model of Huntington's disease.
[So] Source:PLoS One;12(9):e0184580, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hereditary Huntington's disease (HD) is associated with progressive motor, cognitive and psychiatric symptoms. A primary consequence of the HD mutation is the preferential loss of medium spiny projection cells with relative sparing of local interneurons in the striatum. In addition, among GABAergic striatal projection cells, indirect pathway cells expressing D2 dopamine receptors are lost earlier than direct pathway cells expressing D1 receptors. To test in vivo the functional integrity of direct and indirect pathways as well as interneurons in the striatum of male R6/1 transgenic mice, we assessed their c-Fos expression levels induced by a striatal-dependent cognitive task and compared them with age-matched wild-type littermates. We found a significant increase of c-Fos+ nuclei in the dorsomedial striatum, and this only at 2 months, when our HD mouse model is still pre-motor symptomatic, the increase disappearing with symptom manifestation. Contrary to our expectation, the indirect pathway projection neurons did not undergo any severer changes of c-Fos expression regardless of age in R6/1 mice. We also found a decreased activation of interneurons that express parvalbumin in the dorsomedial striatum at both presymptomatic and symptomatic ages. Finally, analysis of c-Fos expression in extended brain regions involved in the cognitive learning used in our study, demonstrates, throughout ages studied, changes in the functional connectivity between regions in the transgenic mice. Further analysis of the cellular and molecular changes underlying the transient striatal hyperactivity in the HD mice may help to understand the mechanisms involved in the disease onset.
[Mh] Termos MeSH primário: Condicionamento Operante/fisiologia
Corpo Estriado/metabolismo
Doença de Huntington/metabolismo
Neurônios/metabolismo
[Mh] Termos MeSH secundário: Animais
Corpo Estriado/patologia
Modelos Animais de Doenças
Progressão da Doença
Doença de Huntington/patologia
Masculino
Camundongos Transgênicos
Atividade Motora/fisiologia
Vias Neurais/metabolismo
Vias Neurais/patologia
Neurônios/patologia
Sintomas Prodrômicos
Proteínas Proto-Oncogênicas c-fos/metabolismo
Distribuição Aleatória
Receptores de Dopamina D1/metabolismo
Receptores de Dopamina D2/metabolismo
Convulsões/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DRD2 protein, rat); 0 (Proto-Oncogene Proteins c-fos); 0 (Receptors, Dopamine D1); 0 (Receptors, Dopamine D2)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184580


  10 / 10574 MEDLINE  
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[PMID]:28920889
[Au] Autor:Wild EJ; Tabrizi SJ
[Ad] Endereço:Huntington's Disease Centre, University College London Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, UK. Electronic address: e.wild@ucl.ac.uk.
[Ti] Título:Therapies targeting DNA and RNA in Huntington's disease.
[So] Source:Lancet Neurol;16(10):837-847, 2017 Oct.
[Is] ISSN:1474-4465
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:No disease-slowing treatment exists for Huntington's disease, but its monogenic inheritance makes it an appealing candidate for the development of therapies targeting processes close to its genetic cause. Huntington's disease is caused by CAG repeat expansions in the HTT gene, which encodes the huntingtin protein; development of therapies to target HTT transcription and the translation of its mRNA is therefore an area of intense investigation. Huntingtin-lowering strategies include antisense oligonucleotides and RNA interference targeting mRNA, and zinc finger transcriptional repressors and CRISPR-Cas9 methods aiming to reduce transcription by targeting DNA. An intrathecally delivered antisense oligonucleotide that aims to lower huntingtin is now well into its first human clinical trial, with other antisense oligonucleotides expected to enter trials in the next 1-2 years and virally delivered RNA interference and zinc finger transcriptional repressors in advanced testing in animal models. Recent advances in the design and delivery of therapies to target HTT RNA and DNA are expected to improve their efficacy, safety, tolerability, and duration of effect in future studies.
[Mh] Termos MeSH primário: Terapia Biológica/métodos
DNA
Proteína Huntingtina
Doença de Huntington/terapia
RNA
[Mh] Termos MeSH secundário: Animais
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Huntingtin Protein); 63231-63-0 (RNA); 9007-49-2 (DNA)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171122
[Lr] Data última revisão:
171122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170919
[St] Status:MEDLINE



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