Base de dados : MEDLINE
Pesquisa : C23.550.369 [Categoria DeCS]
Referências encontradas : 4007 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 401 ir para página                         

  1 / 4007 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29489692
[Au] Autor:Hong HN; Shim JH; Won YJ; Yoo JY; Hwang CH
[Ad] Endereço:Department of Anatomy.
[Ti] Título:Therapeutic time window for the effects of erythropoietin on astrogliosis and neurite outgrowth in an in vitro model of spinal cord injury.
[So] Source:Medicine (Baltimore);97(9):e9913, 2018 Mar.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The objective of this study was to investigate the underlying molecular mechanisms and the therapeutic time window for preventing astrogliosis with erythropoietin (EPO) treatment after in vitro modeled spinal cord injury (SCI). METHODS: Cultured rat spinal cord astrocytes were treated with kainate and scratching to generate an in vitro model of SCI. EPO (100U/mL or 300U/mL) was added immediately or 2, 4, or 8 hours after injury. Some cultures were also treated with AG490, an inhibitor of the EPO-EPO receptor (EpoR) pathway mediator Janus kinase 2 (JAK2). To evaluate neurite extension, rat embryonic spinal cord neurons were seeded onto astrocyte cultures and treated with EPO immediately after injury in the presence or absence of anti-EpoR antibody. RESULTS: EPO treatment at up to 8 hours after injury reduced the expression of axonal growth inhibiting molecules (glial fibrillary acidic protein, vimentin, and chondroitin sulfate proteoglycan), cytoskeletal regulatory proteins (Rho-associated protein kinase and ephephrin A4), and proinflammatory cytokines (tumor necrosis factor-alpha, transforming growth factor-beta, and phosphorylated-Smad3) in a dosedependent manner (P < .001). Most effects peaked with EPO treatment 2-4hours after injury. Additionally, EPO treatment up to 4 hours after injury promoted expression of the EpoR (>2-fold) and JAK2 (>3-fold) in a dose-dependent manner (P < .001), whereas co-treatment with AG490 precluded these effects (P < .001). EPO treatment up to 4hours after injury also enhanced axonal b-III tubulin-immunoreactivity (>12-fold), and this effect was precluded by co-treatment with an anti-EpoR antibody (P < .001). CONCLUSIONS: EPO treatment within 8 hours after injury reduced astrogliosis, and EPO treatment within 4 hours promoted neurite outgrowth. EPO therapy immediately after spinal cord injury may regulate glia to generate an environment permissive of axonal regeneration.
[Mh] Termos MeSH primário: Eritropoetina/administração & dosagem
Gliose/tratamento farmacológico
Crescimento Neuronal/efeitos dos fármacos
Traumatismos da Medula Espinal/tratamento farmacológico
Tempo para o Tratamento
[Mh] Termos MeSH secundário: Animais
Astrócitos
Axônios/efeitos dos fármacos
Células Cultivadas
Esquema de Medicação
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
11096-26-7 (Erythropoietin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180301
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009913


  2 / 4007 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27778404
[Au] Autor:Menzel L; Kleber L; Friedrich C; Hummel R; Dangel L; Winter J; Schmitz K; Tegeder I; Schäfer MK
[Ad] Endereço:Department of Anesthesiology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
[Ti] Título:Progranulin protects against exaggerated axonal injury and astrogliosis following traumatic brain injury.
[So] Source:Glia;65(2):278-292, 2017 02.
[Is] ISSN:1098-1136
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In response to traumatic brain injury (TBI) microglia/macrophages and astrocytes release inflammatory mediators with dual effects on secondary brain damage progression. The neurotrophic and anti-inflammatory glycoprotein progranulin (PGRN) attenuates neuronal damage and microglia/macrophage activation in brain injury but mechanisms are still elusive. Here, we studied histopathology, neurology and gene expression of inflammatory markers in PGRN-deficient mice (Grn ) 24 h and 5 days after experimental TBI. Grn mice displayed increased perilesional axonal injury even though the overall brain tissue loss and neurological consequences were similar to wild-type mice. Brain inflammation was elevated in Grn mice as reflected by increased transcription of pro-inflammatory cytokines TNFα, IL-1ß, IL-6, and decreased transcription of the anti-inflammatory cytokine IL-10. However, numbers of Iba1 microglia/macrophages and immigrated CD45 leukocytes were similar at perilesional sites while determination of IgG extravasation suggested stronger impairment of blood brain barrier integrity in Grn compared to wild-type mice. Most strikingly, Grn mice displayed exaggerated astrogliosis 5 days after TBI as demonstrated by anti-GFAP immunohistochemistry and immunoblot. GFAP astrocytes at perilesional sites were immunolabelled for iNOS and TNFα suggesting that pro-inflammatory activation of astrocytes was attenuated by PGRN. Accordingly, recombinant PGRN (rPGRN) attenuated LPS- and cytokine-evoked iNOS and TNFα mRNA expression in cultured astrocytes. Moreover, intracerebroventricular administration of rPGRN immediately before trauma reduced brain damage and neurological deficits, and restored normal levels of cytokine transcription, axonal injury and astrogliosis 5 days after TBI in Grn mice. Our results show that endogenous and recombinant PGRN limit axonal injury and astrogliosis and suggest therapeutic potential of PGRN in TBI. GLIA 2017;65:278-292.
[Mh] Termos MeSH primário: Axônios/patologia
Lesões Encefálicas Traumáticas/complicações
Lesões Encefálicas Traumáticas/patologia
Gliose/etiologia
Gliose/prevenção & controle
Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Astrócitos/efeitos dos fármacos
Astrócitos/patologia
Axônios/metabolismo
Barreira Hematoencefálica/patologia
Proteínas de Ligação ao Cálcio/metabolismo
Células Cultivadas
Citocinas/genética
Citocinas/metabolismo
Modelos Animais de Doenças
Expressão Gênica/efeitos dos fármacos
Expressão Gênica/genética
Regulação da Expressão Gênica/efeitos dos fármacos
Regulação da Expressão Gênica/genética
Gliose/patologia
Peptídeos e Proteínas de Sinalização Intercelular/genética
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
Lipopolissacarídeos/farmacologia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Proteínas dos Microfilamentos/metabolismo
Proteínas do Tecido Nervoso/metabolismo
Doenças do Sistema Nervoso/etiologia
Doenças do Sistema Nervoso/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aif1 protein, mouse); 0 (Calcium-Binding Proteins); 0 (Cytokines); 0 (Grn protein, mouse); 0 (Intercellular Signaling Peptides and Proteins); 0 (Lipopolysaccharides); 0 (Microfilament Proteins); 0 (Nerve Tissue Proteins)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1002/glia.23091


  3 / 4007 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29216449
[Au] Autor:Liu CC; Zhao N; Fu Y; Wang N; Linares C; Tsai CW; Bu G
[Ad] Endereço:Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA. Electronic address: liu.chiachen@mayo.edu.
[Ti] Título:ApoE4 Accelerates Early Seeding of Amyloid Pathology.
[So] Source:Neuron;96(5):1024-1032.e3, 2017 Dec 06.
[Is] ISSN:1097-4199
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Accumulation and aggregation of amyloid-ß (Aß) in the brain is an initiating step in the pathogenesis of Alzheimer's disease (AD). The ε4 allele of apolipoprotein E (apoE) gene is the strongest genetic risk factor for late-onset AD. Although there is strong evidence showing that apoE4 enhances amyloid pathology, it is not clear what the critical stage(s) is during amyloid development in which apoE4 has the strongest impact. Using apoE inducible mouse models, we show that increased expression of astrocytic apoE4, but not apoE3, during the seeding stage of amyloid development enhanced amyloid deposition and neuritic dystrophy in amyloid model mice. ApoE4, but not apoE3, significantly increased brain Aß half-life measured by in vivo microdialysis. Furthermore, apoE4 expression increased whereas apoE3 reduced amyloid-related gliosis in the mouse brains. Together, our results demonstrate that apoE4 has the greatest impact on amyloid during the seeding stage, likely by perturbing Aß clearance and enhancing Aß aggregation.
[Mh] Termos MeSH primário: Amiloidose/patologia
Apolipoproteína E4/farmacologia
[Mh] Termos MeSH secundário: Doença de Alzheimer/patologia
Amiloidose/genética
Animais
Apolipoproteína E3/farmacologia
Astrócitos/efeitos dos fármacos
Astrócitos/metabolismo
Astrócitos/patologia
Encéfalo/patologia
Técnicas de Introdução de Genes
Gliose/patologia
Seres Humanos
Camundongos
Camundongos Transgênicos
Neuritos/efeitos dos fármacos
Neuritos/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Apolipoprotein E3); 0 (Apolipoprotein E4)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180121
[Lr] Data última revisão:
180121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE


  4 / 4007 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28870788
[Au] Autor:Zawaski JA; Sabek OM; Voicu H; Eastwood Leung HC; Gaber MW
[Ad] Endereço:Department of Pediatrics, Baylor College of Medicine, Houston, Texas; Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas.
[Ti] Título:Effect of Brain Tumor Presence During Radiation on Tissue Toxicity: Transcriptomic and Metabolic Changes.
[So] Source:Int J Radiat Oncol Biol Phys;99(4):983-993, 2017 Nov 15.
[Is] ISSN:1879-355X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Radiation therapy (RT) causes functional and transcriptomic changes in the brain; however, most studies have been carried out in normal rodent brains. Here, the long-term effect of irradiation and tumor presence during radiation was investigated. METHODS AND MATERIALS: Male Wistar rats ∼7 weeks old were divided into 3 groups: sham implant, RT+sham implant, and RT+tumor implant (C6 glioma). Hypofractionated irradiation (8 or 6 Gy/day for 5 days) was localized to a 1-cm strip of cranium starting 5 days after implantation, resulting in complete tumor regression and prolonged survival. Biopsy of tissue was performed in the implant area 65 days after implantation. RNA was hybridized to GeneChip Rat Exon 1.0 ST array. Data were analyzed using significant analysis of microarrays and ingenuity pathway analysis. H magnetic resonance spectroscopy ( H-MRS) imaging was performed in the implantation site 65 to 70 days after implantation using a 9.4 T Biospec magnetic resonance imaging scanner with a quadrature rat brain array. Immunohistochemical staining for astrogliosis, HMG-CoA synthase 2, γ-aminobutyric acid (GABA) and taurine was performed at ∼65 days after implantation. RESULTS: Eighty-four genes had a false discovery rate <3.5%. We compared RT+tumor implant with RT+sham implant animals. The tumor presence affected networks associated with cancer/cell morphology/tissue morphology. H-MRS showed significant reduction in taurine levels (P<.04) at the implantation site in both groups. However, the RT+tumor group also showed significant increase in levels of neurotransmitter GABA (P=.02). Hippocampal taurine levels were only significantly reduced in the RT+tumor group (P=.03). HMG-CoA synthase 2, GABA and taurine levels were confirmed using staining. Glial fibrillary acidic protein staining demonstrated a significant increase in inflammation that was heightened in the RT+tumor group. CONCLUSIONS: Our data indicate that tumor presence during radiation significantly affects long-term functional transcriptomics landscape and neurotransmitter levels at the tumor implantation site/normal tissue, accompanied by increased inflammation (astrogliosis).
[Mh] Termos MeSH primário: Neoplasias Encefálicas/radioterapia
Encéfalo/efeitos da radiação
Glioma/radioterapia
Neurotransmissores/análise
Lesões Experimentais por Radiação/metabolismo
[Mh] Termos MeSH secundário: Aloenxertos
Animais
Biópsia
Encéfalo/metabolismo
Encéfalo/patologia
Neoplasias Encefálicas/química
Neoplasias Encefálicas/patologia
Radioterapia Hipofracionada
Perfilação da Expressão Gênica
Glioma/química
Glioma/patologia
Gliose/metabolismo
Gliose/patologia
Hipocampo/química
Hipocampo/patologia
Hipocampo/efeitos da radiação
Hidroximetilglutaril-CoA Sintase/análise
Imagem por Ressonância Magnética/métodos
Espectroscopia de Ressonância Magnética
Masculino
Transplante de Neoplasias
Neurotransmissores/metabolismo
Lesões Experimentais por Radiação/patologia
Ratos
Ratos Wistar
Taurina/análise
Fatores de Tempo
Análise Serial de Tecidos/métodos
Ácido gama-Aminobutírico/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Neurotransmitter Agents); 1EQV5MLY3D (Taurine); 56-12-2 (gamma-Aminobutyric Acid); EC 2.3.3.10 (Hydroxymethylglutaryl-CoA Synthase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170906
[St] Status:MEDLINE


  5 / 4007 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28867578
[Au] Autor:Rostami F; Javan M; Moghimi A; Haddad-Mashadrizeh A; Fereidoni M
[Ad] Endereço:Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
[Ti] Título:Streptozotocin-induced hippocampal astrogliosis and insulin signaling malfunction as experimental scales for subclinical sporadic Alzheimer model.
[So] Source:Life Sci;188:172-185, 2017 Nov 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: Insulin signaling malfunction has recently been suggested as a preliminary event involved in the etiology of Sporadic Alzheimer's disease (SAD). In order to develop insulin resistance-related SAD model, rats were treated with streptozotocin, intracerebroventricularly (icv-STZ). Nevertheless, given the lack of knowledge regarding sub-clinical stages of SAD, the current challenging issue is establishing a practical pre-clinical SAD model. Despite some proposed mechanisms, such as insulin malfunction, neuroinflammation, and gliosis, icv-STZ mechanism of action is not fully understood yet and Streptozotocin-induced rat model of Alzheimer has still major shortcomings. MAIN METHODS: Using three STZ doses (0.5, 1, and 3mg/kg) and three testing time (short-term, medium-term and long-term), we sought the best dose of STZ in order to mimic the characteristic feature of sAD in rats. So, we conducted a series of fifteen-week follow-up cognitive and non-cognitive studies. Besides, IR, tau and ChAT mRNA levels were measured, along with histological analysis of astrocyte, dark neuron numbers, and pyramidal layer thickness, in order to compare the effects of different doses of icv-STZ. KEY FINDINGS: STZ 3mg/kg caused cognitive and insulin signaling disturbance from the very first testing-time. STZ1-injected animals, however, showed an augmented hippocampal astrocyte numbers in a short time; they, also, were diagnosed with disturbed insulin signaling in medium-term post icv-STZ-injection. Moreover, behavioral, molecular and histological impairments induced by 0.5mg/kg icv-STZ were slowly progressing in comparison to high doses of STZ. SIGNIFICANCE: STZ1 and 0.5mg/kg-treated animals are, respectively, suggested as a suitable experimental model of MCI, and sub-clinical stage.
[Mh] Termos MeSH primário: Doença de Alzheimer/diagnóstico
Gliose/patologia
Hipocampo/patologia
Resistência à Insulina
Insulina/metabolismo
Sintomas Prodrômicos
Estreptozocina/efeitos adversos
[Mh] Termos MeSH secundário: Animais
Astrócitos/patologia
Colina O-Acetiltransferase/biossíntese
Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Comportamento Exploratório/efeitos dos fármacos
Gliose/induzido quimicamente
Infusões Intraventriculares
Masculino
Aprendizagem em Labirinto/efeitos dos fármacos
Neurônios/patologia
Ratos
Receptor de Insulina/biossíntese
Recognição (Psicologia)/efeitos dos fármacos
Teste de Desempenho do Rota-Rod
Estreptozocina/administração & dosagem
Fatores de Tempo
Proteínas tau/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Insulin); 0 (tau Proteins); 5W494URQ81 (Streptozocin); EC 2.3.1.6 (Choline O-Acetyltransferase); EC 2.7.10.1 (Receptor, Insulin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170905
[St] Status:MEDLINE


  6 / 4007 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28822786
[Au] Autor:Chang KT; Lin YL; Lin CT; Hong CJ; Tsai MJ; Huang WC; Shih YH; Lee YY; Cheng H; Huang MC
[Ad] Endereço:Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Neural Regeneration Laboratory, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
[Ti] Título:Leptin is essential for microglial activation and neuropathic pain after preganglionic cervical root avulsion.
[So] Source:Life Sci;187:31-41, 2017 Oct 15.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: Preganglionic cervical root avulsion (PCRA) affects both the peripheral and central nervous systems and is often associated with neuropathic pain. Unlike peripheral nerve injuries (PNI), central lesions caused by disruption of cervical roots from the spinal cord following PCRA contribute to the generation of neuropathic pain. Leptin is involved in the development of neuropathic pain after PNI by affecting neurons. However, whether leptin is involved in microglial activation leading to neuropathic pain after PCRA is unknown. MAIN METHODS: Preganglionic avulsion of the left 6 -8 cervical roots was performed in C57B/6J mice and leptin-deficient mice. A leptin antagonist or leptin was administered to C57B/6J mice and leptin-deficient mice after injury, respectively. The expression pattern of spinal and supraspinal microglia was examined by immunofluorescent staining. Von Frey filaments were used to test pain sensitivity. KEY FINDINGS: Leptin is essential for the development of neuropathic pain after PCRA. Allodynia was absent in the leptin-deficient mice and the mice administered the leptin antagonist. We also found that leptin deficiency or the administration of its antagonist inhibited the development of microgliosis in the dorsal horn and brainstem. Furthermore, increase in the expression of CD86 and iNOS, and Wallerian degeneration were noted in the spinal cord. The administration of exogenous leptin to leptin-deficient mice reversed these effects. SIGNIFICANCE: We concluded that leptin is involved in the proliferation and activation of microglia, which in turn enhances the development of neuropathic pain. Blocking the effects of leptin might be a target for the treatment of neuropathic pain after PCRA.
[Mh] Termos MeSH primário: Fratura Avulsão/fisiopatologia
Leptina/fisiologia
Microglia/fisiologia
Neuralgia/prevenção & controle
[Mh] Termos MeSH secundário: Animais
Antígeno B7-2/biossíntese
Tronco Encefálico/efeitos dos fármacos
Tronco Encefálico/patologia
Proliferação Celular/fisiologia
Medula Cervical/lesões
Feminino
Fratura Avulsão/complicações
Fratura Avulsão/patologia
Gliose/prevenção & controle
Leptina/antagonistas & inibidores
Leptina/genética
Leptina/farmacologia
Masculino
Camundongos
Camundongos Transgênicos
Microglia/efeitos dos fármacos
Neuralgia/complicações
Óxido Nítrico Sintase Tipo II/biossíntese
Medição da Dor/efeitos dos fármacos
Medula Espinal/efeitos dos fármacos
Medula Espinal/metabolismo
Medula Espinal/patologia
Corno Dorsal da Medula Espinal/efeitos dos fármacos
Corno Dorsal da Medula Espinal/patologia
Degeneração Walleriana/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (B7-2 Antigen); 0 (Leptin); EC 1.14.13.39 (Nitric Oxide Synthase Type II); EC 1.14.13.39 (Nos2 protein, mouse)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170821
[St] Status:MEDLINE


  7 / 4007 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28715425
[Au] Autor:Dietrich P; Johnson IM; Alli S; Dragatsis I
[Ad] Endereço:Department of Physiology, The University of Tennessee, Health Science Center, Memphis, Tennessee, United States of America.
[Ti] Título:Elimination of huntingtin in the adult mouse leads to progressive behavioral deficits, bilateral thalamic calcification, and altered brain iron homeostasis.
[So] Source:PLoS Genet;13(7):e1006846, 2017 Jul.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Huntington's Disease (HD) is an autosomal dominant progressive neurodegenerative disorder characterized by cognitive, behavioral and motor dysfunctions. HD is caused by a CAG repeat expansion in exon 1 of the HD gene that is translated into an expanded polyglutamine tract in the encoded protein, huntingtin (HTT). While the most significant neuropathology of HD occurs in the striatum, other brain regions are also affected and play an important role in HD pathology. To date there is no cure for HD, and recently strategies aiming at silencing HTT expression have been initiated as possible therapeutics for HD. However, the essential functions of HTT in the adult brain are currently unknown and hence the consequence of sustained suppression of HTT expression is unpredictable and can potentially be deleterious. Using the Cre-loxP system of recombination, we conditionally inactivated the mouse HD gene homologue at 3, 6 and 9 months of age. Here we show that elimination of Htt expression in the adult mouse results in behavioral deficits, progressive neuropathological changes including bilateral thalamic calcification, and altered brain iron homeostasis.
[Mh] Termos MeSH primário: Encéfalo/fisiopatologia
Calcinose/genética
Proteína Huntingtina/genética
Doença de Huntington/genética
Ferro/metabolismo
[Mh] Termos MeSH secundário: Animais
Comportamento Animal
Encéfalo/metabolismo
Encefalopatias/genética
Encefalopatias/patologia
Calcinose/diagnóstico
Calcinose/patologia
Modelos Animais de Doenças
Éxons
Feminino
Regulação da Expressão Gênica
Técnicas de Genotipagem
Gliose/diagnóstico
Gliose/genética
Homeostase
Proteína Huntingtina/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
RNA Ribossômico 18S/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Huntingtin Protein); 0 (RNA, Ribosomal, 18S); E1UOL152H7 (Iron)
[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:170718
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006846


  8 / 4007 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28714867
[Au] Autor:Perez EJ; Tapanes SA; Loris ZB; Balu DT; Sick TJ; Coyle JT; Liebl DJ
[Ad] Endereço:The Miami Project to Cure Paralysis, Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, Florida, USA.
[Ti] Título:Enhanced astrocytic d-serine underlies synaptic damage after traumatic brain injury.
[So] Source:J Clin Invest;127(8):3114-3125, 2017 Aug 01.
[Is] ISSN:1558-8238
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:After traumatic brain injury (TBI), glial cells have both beneficial and deleterious roles in injury progression and recovery. However, few studies have examined the influence of reactive astrocytes in the tripartite synapse following TBI. Here, we have demonstrated that hippocampal synaptic damage caused by controlled cortical impact (CCI) injury in mice results in a switch from neuronal to astrocytic d-serine release. Under nonpathological conditions, d-serine functions as a neurotransmitter and coagonist for NMDA receptors and is involved in mediating synaptic plasticity. The phasic release of neuronal d-serine is important in maintaining synaptic function, and deficiencies lead to reductions in synaptic function and plasticity. Following CCI injury, hippocampal neurons downregulated d-serine levels, while astrocytes enhanced production and release of d-serine. We further determined that this switch in the cellular source of d-serine, together with the release of basal levels of glutamate, contributes to synaptic damage and dysfunction. Astrocyte-specific elimination of the astrocytic d-serine-synthesizing enzyme serine racemase after CCI injury improved synaptic plasticity, brain oscillations, and learning behavior. We conclude that the enhanced tonic release of d-serine from astrocytes after TBI underlies much of the synaptic damage associated with brain injury.
[Mh] Termos MeSH primário: Astrócitos/citologia
Lesões Encefálicas Traumáticas/metabolismo
Serina/metabolismo
Sinapses/metabolismo
[Mh] Termos MeSH secundário: Animais
Encéfalo/metabolismo
Lesões Encefálicas/metabolismo
Células Cultivadas
Gliose
Ácido Glutâmico/metabolismo
Hipocampo/metabolismo
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Plasticidade Neuronal/fisiologia
Neurônios/metabolismo
Receptores de N-Metil-D-Aspartato/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, N-Methyl-D-Aspartate); 3KX376GY7L (Glutamic Acid); 452VLY9402 (Serine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170718
[St] Status:MEDLINE


  9 / 4007 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28642233
[Au] Autor:Borroni E; Bohrmann B; Grueninger F; Prinssen E; Nave S; Loetscher H; Chinta SJ; Rajagopalan S; Rane A; Siddiqui A; Ellenbroek B; Messer J; Pähler A; Andersen JK; Wyler R; Cesura AM
[Ad] Endereço:Roche Innovation Center Basel, Pharma Research and Early Development, F. Hoffmann-La Roche Ltd., Basel, Switzerland (E.B., B.B., F.G., E.P., S.N., H.L., J.M., A.P., and R.W.); Buck Institute for Research on Aging, Novato, California (S.C., S.R., A.R., A.S., and J.A.); and Evotec International GmbH,
[Ti] Título:Sembragiline: A Novel, Selective Monoamine Oxidase Type B Inhibitor for the Treatment of Alzheimer's Disease.
[So] Source:J Pharmacol Exp Ther;362(3):413-423, 2017 Sep.
[Is] ISSN:1521-0103
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Monoamine oxidase B (MAO-B) has been implicated in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative disorders. Increased MAO-B expression in astroglia has been observed adjacent to amyloid plaques in AD patient brains. This phenomenon is hypothesized to lead to increased production of hydrogen peroxide and reactive oxygen species (ROS), thereby contributing to AD pathology. Therefore, reduction of ROS-induced oxidative stress via inhibition of MAO-B activity may delay the progression of the disease. In the present study we report the pharmacological properties of sembragiline, a novel selective MAO-B inhibitor specifically developed for the treatment of AD, and on its effect on ROS-mediated neuronal injury and astrogliosis in MAO-B transgenic animals. Sembragiline showed potent and long-lasting MAO-B-selective inhibition and did not inhibit MAO-A at doses where full inhibition of MAO-B was observed. Such selectivity should translate into a favorable clinical safety profile. Indeed, sembragiline neither induced the serotonin syndrome when administered together with the serotonin precursor l-5-hydroxytryptophan in combination with antidepressants such as fluoxetine, nor potentiated the pressor effect of tyramine. Additionally, in experiments using a transgenic animal model conditionally overexpressing MAO-B in astroglia, sembragiline protected against neuronal loss and reduced both ROS formation and reactive astrogliosis. Taken together, these findings warrant further investigation of the potential therapeutic benefit of MAO-B inhibitors in patients with AD and other neurologic disorders.
[Mh] Termos MeSH primário: Acetamidas/uso terapêutico
Doença de Alzheimer/tratamento farmacológico
Inibidores da Monoaminoxidase/uso terapêutico
Monoaminoxidase/efeitos dos fármacos
Pirrolidinonas/uso terapêutico
[Mh] Termos MeSH secundário: 5-Hidroxitriptofano/farmacologia
Acetamidas/farmacocinética
Animais
Astrócitos/efeitos dos fármacos
Astrócitos/metabolismo
Gliose/tratamento farmacológico
Gliose/patologia
Seres Humanos
Hipertensão/induzido quimicamente
Hipertensão/prevenção & controle
Masculino
Monoaminoxidase/genética
Monoaminoxidase/metabolismo
Inibidores da Monoaminoxidase/farmacocinética
Atividade Motora/efeitos dos fármacos
Neurotransmissores/metabolismo
Pirrolidinonas/farmacocinética
Ratos
Ratos Transgênicos
Espécies Reativas de Oxigênio/metabolismo
Especificidade por Substrato
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetamides); 0 (Monoamine Oxidase Inhibitors); 0 (Neurotransmitter Agents); 0 (Pyrrolidinones); 0 (Reactive Oxygen Species); 0 (sembragiline); C1LJO185Q9 (5-Hydroxytryptophan); EC 1.4.3.4 (Monoamine Oxidase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170624
[St] Status:MEDLINE
[do] DOI:10.1124/jpet.117.241653


  10 / 4007 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28628761
[Au] Autor:Vessey KA; Gu BJ; Jobling AI; Phipps JA; Greferath U; Tran MX; Dixon MA; Baird PN; Guymer RH; Wiley JS; Fletcher EL
[Ad] Endereço:Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia.
[Ti] Título:Loss of Function of P2X7 Receptor Scavenger Activity in Aging Mice: A Novel Model for Investigating the Early Pathogenesis of Age-Related Macular Degeneration.
[So] Source:Am J Pathol;187(8):1670-1685, 2017 Aug.
[Is] ISSN:1525-2191
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Age-related macular degeneration (AMD) is a leading cause of irreversible, severe vision loss in Western countries. Recently, we identified a novel pathway involving P2X7 receptor scavenger function expressed on ocular immune cells as a risk factor for advanced AMD. In this study, we investigate the effect of loss of P2X7 receptor function on retinal structure and function during aging. P2X7-null and wild-type C57bl6J mice were investigated at 4, 12, and 18 months of age for macrophage phagocytosis activity, ocular histological changes, and retinal function. Phagocytosis activity of blood-borne macrophages decreased with age at 18 months in the wild-type mouse. Lack of P2X7 receptor function reduced phagocytosis at all ages compared to wild-type mice. At 12 months of age, P2X7-null mice had thickening of Bruchs membrane and retinal pigment epithelium dysfunction. By 18 months of age, P2X7-null mice displayed phenotypic characteristics consistent with early AMD, including Bruchs membrane thickening, retinal pigment epithelium cell loss, retinal functional deficits, and signs of subretinal inflammation. Our present study shows that loss of function of the P2X7 receptor in mice induces retinal changes representing characteristics of early AMD, providing a valuable model for investigating the role of scavenger receptor function and the immune system in the development of this age-related disease.
[Mh] Termos MeSH primário: Envelhecimento/metabolismo
Macrófagos/metabolismo
Degeneração Macular/metabolismo
Receptores Purinérgicos P2X7/metabolismo
Retina/metabolismo
[Mh] Termos MeSH secundário: Envelhecimento/patologia
Animais
Modelos Animais de Doenças
Células Ependimogliais/metabolismo
Células Ependimogliais/patologia
Gliose/genética
Gliose/metabolismo
Gliose/patologia
Macrófagos/patologia
Degeneração Macular/genética
Degeneração Macular/patologia
Camundongos
Camundongos Knockout
Fagocitose/fisiologia
Receptores Purinérgicos P2X7/genética
Retina/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Purinergic P2X7)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170620
[St] Status:MEDLINE



página 1 de 401 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde