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  1 / 109 MEDLINE  
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[PMID]:28712654
[Au] Autor:Favuzzi E; Marques-Smith A; Deogracias R; Winterflood CM; Sánchez-Aguilera A; Mantoan L; Maeso P; Fernandes C; Ewers H; Rico B
[Ad] Endereço:Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE1 1UL, UK; MRC Centre for Neurodevelopmental Disorders, King's College London, London, SE1 1UL, UK; Instituto de Neurociencias, Consejo Superior de Investigaciones Científica
[Ti] Título:Activity-Dependent Gating of Parvalbumin Interneuron Function by the Perineuronal Net Protein Brevican.
[So] Source:Neuron;95(3):639-655.e10, 2017 Aug 02.
[Is] ISSN:1097-4199
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Activity-dependent neuronal plasticity is a fundamental mechanism through which the nervous system adapts to sensory experience. Several lines of evidence suggest that parvalbumin (PV+) interneurons are essential in this process, but the molecular mechanisms underlying the influence of experience on interneuron plasticity remain poorly understood. Perineuronal nets (PNNs) enwrapping PV+ cells are long-standing candidates for playing such a role, yet their precise contribution has remained elusive. We show that the PNN protein Brevican is a critical regulator of interneuron plasticity. We find that Brevican simultaneously controls cellular and synaptic forms of plasticity in PV+ cells by regulating the localization of potassium channels and AMPA receptors, respectively. By modulating Brevican levels, experience introduces precise molecular and cellular modifications in PV+ cells that are required for learning and memory. These findings uncover a molecular program through which a PNN protein facilitates appropriate behavioral responses to experience by dynamically gating PV+ interneuron function.
[Mh] Termos MeSH primário: Brevicam/metabolismo
Neurônios GABAérgicos/metabolismo
Interneurônios/metabolismo
Memória/fisiologia
Parvalbuminas/metabolismo
[Mh] Termos MeSH secundário: Animais
Matriz Extracelular/metabolismo
Camundongos
Plasticidade Neuronal/fisiologia
Córtex Visual/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Brevican); 0 (Parvalbumins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170914
[Lr] Data última revisão:
170914
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170718
[St] Status:MEDLINE


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[PMID]:27529670
[Au] Autor:Virga J; Bognár L; Hortobágyi T; Zahuczky G; Csosz É; Kalló G; Tóth J; Hutóczki G; Reményi-Puskár J; Steiner L; Klekner A
[Ad] Endereço:Department of Neurosurgery, University of Debrecen Clinical Center, Debrecen, Hungary.
[Ti] Título:Prognostic Role of the Expression of Invasion-Related Molecules in Glioblastoma.
[So] Source:J Neurol Surg A Cent Eur Neurosurg;78(1):12-19, 2017 Jan.
[Is] ISSN:2193-6323
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Glioblastoma multiforme (GBM) is the most common malignant disease of the central nervous system. Its prognosis is unfavorable, and the median overall survival of patients is 16 to 24 months. The main cause of the poor survival data are the extensive invasion of cancer cells to the neighboring parenchyma, thus leading to inevitable local recurrence. The extracellular matrix (ECM) is a known factor in tumor invasion, and differences in the ECM of nontumor brain and glioblastoma has been proven. In this research, 20 invasion-related expressions of ECM components were determined in 26 GBM flash-frozen samples using quantitative reverse transcription-polymerase chain reaction and proteomic measurements. Expression data were then set against the survival data of the patients. Significant alterations between groups with different survival rates could not be established in the individual evaluation of the expression level of the selected molecules. However, statistical analysis of the expression pattern of invasion-related molecules revealed a correlation with prognosis. The positive predictive values of the messenger RNA (mRNA) and the proteomic expression studies were 0.85 and 0.89, respectively. The receiver operation characteristic value was 0.775 for the mRNA expression data and 0.875 for the protein expression data. Furthermore, a group of molecules, including brevican, cadherin-12, integrin ß1, integrin α3, laminin α4, and laminin ß1, that play a prominent role in invasion were identified. Joint assessment of the expression of invasion-related molecules provides a specific invasion spectrum of the tumor that correlates with the survival of glioblastoma patients. Using statistical classifiers enables the adoption of an invasion spectrum as a considerably accurate prognostic factor while gaining predictive information on potential molecular oncotherapeutic targets at the same time.
[Mh] Termos MeSH primário: Neoplasias Encefálicas/metabolismo
Matriz Extracelular/metabolismo
Glioblastoma/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Neoplasias Encefálicas/mortalidade
Neoplasias Encefálicas/patologia
Brevicam/metabolismo
Caderinas/metabolismo
Intervalo Livre de Doença
Matriz Extracelular/patologia
Feminino
Glioblastoma/mortalidade
Glioblastoma/patologia
Seres Humanos
Cadeias alfa de Integrinas/metabolismo
Cadeias beta de Integrinas/metabolismo
Laminina/metabolismo
Masculino
Meia-Idade
Prognóstico
Taxa de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Brevican); 0 (CDH23 protein, human); 0 (Cadherins); 0 (Integrin alpha Chains); 0 (Integrin beta Chains); 0 (LAMA4 protein, human); 0 (LAMB1 protein, human); 0 (Laminin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170615
[Lr] Data última revisão:
170615
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160817
[St] Status:MEDLINE
[do] DOI:10.1055/s-0036-1584920


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[PMID]:26780384
[Au] Autor:Dauth S; Grevesse T; Pantazopoulos H; Campbell PH; Maoz BM; Berretta S; Parker KK
[Ad] Endereço:Disease Biophysics Group, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, 02138.
[Ti] Título:Extracellular matrix protein expression is brain region dependent.
[So] Source:J Comp Neurol;524(7):1309-36, 2016 May 01.
[Is] ISSN:1096-9861
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In the brain, extracellular matrix (ECM) components form networks that contribute to structural and functional diversity. Maladaptive remodeling of ECM networks has been reported in neurodegenerative and psychiatric disorders, suggesting that the brain microenvironment is a dynamic structure. A lack of quantitative information about ECM distribution in the brain hinders an understanding of region-specific ECM functions and the role of ECM in health and disease. We hypothesized that each ECM protein as well as specific ECM structures, such as perineuronal nets (PNNs) and interstitial matrix, are differentially distributed throughout the brain, contributing to the unique structure and function in the various regions of the brain. To test our hypothesis, we quantitatively analyzed the distribution, colocalization, and protein expression of aggrecan, brevican, and tenascin-R throughout the rat brain utilizing immunohistochemistry and mass spectrometry analysis and assessed the effect of aggrecan, brevican, and/or tenascin-R on neurite outgrowth in vitro. We focused on aggrecan, brevican, and tenascin-R as they are especially expressed in the mature brain, and have established roles in brain development, plasticity, and neurite outgrowth. The results revealed a differentiated distribution of all three proteins throughout the brain and indicated that their presence significantly reduces neurite outgrowth in a 3D in vitro environment. These results underline the importance of a unique and complex ECM distribution for brain physiology and suggest that encoding the distribution of distinct ECM proteins throughout the brain will aid in understanding their function in physiology and in turn assist in identifying their role in disease. J. Comp. Neurol. 524:1309-1336, 2016. © 2016 Wiley Periodicals, Inc.
[Mh] Termos MeSH primário: Encéfalo/anatomia & histologia
Encéfalo/metabolismo
Proteínas da Matriz Extracelular/genética
Regulação da Expressão Gênica
[Mh] Termos MeSH secundário: Agrecanas/metabolismo
Análise de Variância
Animais
Animais Recém-Nascidos
Brevicam/metabolismo
Células Cultivadas
Córtex Cerebral/citologia
Proteínas da Matriz Extracelular/metabolismo
Feminino
Imagem Tridimensional
Espectrometria de Massas
Rede Nervosa/metabolismo
Neuritos/metabolismo
Neuroimagem
Neurônios/metabolismo
Neurônios/ultraestrutura
Ratos
Ratos Sprague-Dawley
Tubulina (Proteína)/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Aggrecans); 0 (Brevican); 0 (Extracellular Matrix Proteins); 0 (Tubb3 protein, rat); 0 (Tubulin)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:170115
[Lr] Data última revisão:
170115
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160119
[St] Status:MEDLINE
[do] DOI:10.1002/cne.23965


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[PMID]:26322652
[Au] Autor:Xu X; Li N; Zhu L; Zhou Y; Cheng H
[Ad] Endereço:a Department of Neurosurgery , Jinling Hospital, School of Medicine, Nanjing University , Nanjing , Jiangsu Province , China.
[Ti] Título:Beneficial effects of local profound hypothermia and the possible mechanism after experimental spinal cord injury in rats.
[So] Source:J Spinal Cord Med;39(2):220-8, 2016.
[Is] ISSN:2045-7723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The primary focus of this study was to investigate the effects of local profound hypothermia and to explore the possible mechanism in adult rats with spinal cord injury. STUDY DESIGN AND METHODS: Spinal cord injury models were established by placing aneurysm clips on T10. An epidural perfusion device was applied to maintain a steady temperature (18 °C) for 120 min with gradual rewarming to 37 °C Total hypothermic duration lasted up to about 170 min. The expression of axon regeneration inhibitors was tested by Western blot and real-time PCR. Luxol Fast Blue (LFB) stain and Bielschowsky silver stain were used to observe spinal cord morphology. Motor function of the hind limbs (BBB score) was monitored for 21 days. RESULTS: The expressions of RhoA, ROCK-II, NG2, Neurocan, Brevican, and Nogo-A were downregulated by regional hypothermia (RH) after spinal cord injury. Subsequent observation showed that rats that had received RH had an alleviated demyelinating condition and a greater number of nerve fibers. Furthermore, the RH group achieved higher BBB scores than the spinal cord injury (SCI) group. CONCLUSIONS: Recovery of hind limb function in rats can be promoted by local profound hypothermia; this may be caused by the suppression of axon regeneration inhibitors.
[Mh] Termos MeSH primário: Hipotermia Induzida
Regeneração Nervosa
Traumatismos da Medula Espinal/terapia
[Mh] Termos MeSH secundário: Animais
Axônios/metabolismo
Axônios/fisiologia
Brevicam/genética
Brevicam/metabolismo
Regulação para Baixo
Membro Posterior/inervação
Membro Posterior/fisiologia
Masculino
Neurocam/genética
Neurocam/metabolismo
Proteínas Nogo/genética
Proteínas Nogo/metabolismo
Ratos
Ratos Sprague-Dawley
Recuperação de Função Fisiológica
Traumatismos da Medula Espinal/reabilitação
Quinases Associadas a rho/genética
Quinases Associadas a rho/metabolismo
Proteína rhoA de Ligação ao GTP/genética
Proteína rhoA de Ligação ao GTP/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Brevican); 0 (Neurocan); 0 (Nogo Proteins); EC 2.7.11.1 (rho-Associated Kinases); EC 3.6.5.2 (rhoA GTP-Binding Protein)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:170301
[Lr] Data última revisão:
170301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150901
[St] Status:MEDLINE
[do] DOI:10.1179/2045772315Y.0000000051


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[PMID]:26332441
[Au] Autor:Chen H; He D; Lasek AW
[Ad] Endereço:Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois.
[Ti] Título:Repeated Binge Drinking Increases Perineuronal Nets in the Insular Cortex.
[So] Source:Alcohol Clin Exp Res;39(10):1930-8, 2015 Oct.
[Is] ISSN:1530-0277
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Alcohol exposure leads to changes in the extracellular matrix (ECM) in the brain, which profoundly impacts neuronal plasticity. Perineuronal nets (PNs) are specialized ECM structures that enclose subpopulations of neurons in the cortex. Adolescent exposure to alcohol induces long-lasting increases in the expression of PN components in the cortex in adult mice. However, it has not been determined whether binge alcohol exposure in young adults alters PNs. Here, we examined PNs and their core components in the insula and primary motor cortex after repeated binge-like ethanol (EtOH) consumption in adult mice. METHODS: The 4-day drinking in the dark (DID) procedure was performed in mice for 1 or 6 weeks to model binge alcohol consumption. The impact of EtOH drinking on PNs was examined by fluorescent staining of brain sections using a marker for PNs, Wisteria floribunda agglutinin (WFA). In another set of experiments, cortex was dissected and Western blots and real-time quantitative polymerase chain reaction were performed to evaluate the expression of the PN proteins aggrecan, brevican, and phosphacan. RESULTS: Binge-like EtOH drinking for 6 weeks caused a significant increase in PNs in the insula, as measured by WFA binding. Aggrecan, brevican, and phosphacan protein expression, and aggrecan mRNA expression, were also elevated in the insula after 6 weeks of EtOH drinking. In contrast, expression of PN components did not change after 1 week of DID. The increase in PNs appears to be specific to the insula, because alterations were not observed in the primary motor cortex. CONCLUSIONS: Our results provide the first evidence that insular PNs increase after long-term binge drinking. The insula mediates compulsive alcohol use. As PNs influence neuronal firing and plasticity, increased PNs in the insula after multiple binge cycles may contribute to restricted neuronal plasticity and lead to the development of compulsive alcohol use.
[Mh] Termos MeSH primário: Bebedeira/metabolismo
Córtex Cerebral/efeitos dos fármacos
Etanol/administração & dosagem
Etanol/farmacologia
Matriz Extracelular/efeitos dos fármacos
Neurônios/efeitos dos fármacos
[Mh] Termos MeSH secundário: Agrecanas/biossíntese
Animais
Brevicam/biossíntese
Córtex Cerebral/metabolismo
Masculino
Camundongos
Córtex Motor/efeitos dos fármacos
Córtex Motor/metabolismo
Neurônios/metabolismo
Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Aggrecans); 0 (Brevican); 3K9958V90M (Ethanol); EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 5)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150903
[St] Status:MEDLINE
[do] DOI:10.1111/acer.12847


  6 / 109 MEDLINE  
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[PMID]:26223835
[Au] Autor:Blosa M; Sonntag M; Jäger C; Weigel S; Seeger J; Frischknecht R; Seidenbecher CI; Matthews RT; Arendt T; Rübsamen R; Morawski M
[Ad] Endereço:Paul Flechsig Institute for Brain Research, Faculty of Medicine, University of Leipzig, 04103, Leipzig, Germany.
[Ti] Título:The extracellular matrix molecule brevican is an integral component of the machinery mediating fast synaptic transmission at the calyx of Held.
[So] Source:J Physiol;593(19):4341-60, 2015 Oct 01.
[Is] ISSN:1469-7793
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:KEY POINTS: The proteoglycan brevican is a major component of the extracellular matrix of perineuronal nets and is highly enriched in the perisynaptic space suggesting a role for synaptic transmission. We have introduced the calyx of Held in the auditory brainstem as a model system to study the impact of brevican on dynamics and reliability of synaptic transmission. In vivo extracellular single-unit recordings at the calyx of Held in brevican-deficient mice yielded a significant increase in the action potential (AP) transmission delay and a prolongation of pre- and postsynaptic APs. The changes in dynamics of signal transmission were accompanied by the reduction of presynaptic vGlut1 and ultrastructural changes in the perisynaptic space. These data show that brevican is an important mediator of fast synaptic transmission at the calyx of Held. ABSTRACT: The extracellular matrix is an integral part of the neural tissue. Its most conspicuous manifestation in the brain are the perineuronal nets (PNs) which surround somata and proximal dendrites of distinct neuron types. The chondroitin sulfate proteoglycan brevican is a major component of PNs. In contrast to other PN-comprising proteoglycans (e.g. aggrecan and neurocan), brevican is mainly expressed in the perisynaptic space closely associated with both the pre- and postsynaptic membrane. This specific localization prompted the hypothesis that brevican might play a role in synaptic transmission. In the present study we specifically investigated the role of brevican in synaptic transmission at a central synapse, the calyx of Held in the medial nucleus of the trapezoid body, by the use of in vivo electrophysiology, immunohistochemistry, biochemistry and electron microscopy. In vivo extracellular single-unit recordings were acquired in brevican-deficient mice and the dynamics and reliability of synaptic transmission were compared to wild-type littermates. In knockout mice, the speed of pre-to-postsynaptic action potential (AP) transmission was reduced and the duration of the respective pre- and postsynaptic APs increased. The reliability of signal transmission, however, was not affected by the lack of brevican. The changes in dynamics of signal transmission were accompanied by the reduction of (i) presynaptic vGlut1 and (ii) the size of subsynaptic cavities. The present results suggest an essential role of brevican for the functionality of high-speed synaptic transmission at the calyx of Held.
[Mh] Termos MeSH primário: Brevicam/fisiologia
Transmissão Sináptica/fisiologia
Corpo Trapezoide/fisiologia
[Mh] Termos MeSH secundário: Estimulação Acústica
Potenciais de Ação
Animais
Brevicam/genética
Transportador 2 de Aminoácido Excitatório/metabolismo
Matriz Extracelular
Feminino
Transportador de Glucose Tipo 1/metabolismo
Transportador de Glucose Tipo 2/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Sinapses/fisiologia
Corpo Trapezoide/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bcan protein, mouse); 0 (Brevican); 0 (Excitatory Amino Acid Transporter 2); 0 (Glucose Transporter Type 1); 0 (Glucose Transporter Type 2); 0 (Slc1a2 protein, mouse); 0 (Slc2a1 protein, mouse); 0 (Slc2a2 protein, mouse)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150731
[St] Status:MEDLINE
[do] DOI:10.1113/JP270849


  7 / 109 MEDLINE  
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[PMID]:25225099
[Au] Autor:Valenzuela JC; Heise C; Franken G; Singh J; Schweitzer B; Seidenbecher CI; Frischknecht R
[Ad] Endereço:Department for Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology Magdeburg, Magdeburg, Germany.
[Ti] Título:Hyaluronan-based extracellular matrix under conditions of homeostatic plasticity.
[So] Source:Philos Trans R Soc Lond B Biol Sci;369(1654):20130606, 2014 Oct 19.
[Is] ISSN:1471-2970
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Neuronal networks are balanced by mechanisms of homeostatic plasticity, which adjusts synaptic strength via molecular and morphological changes in the pre- and post-synapse. Here, we wondered whether the hyaluronic acid-based extracellular matrix (ECM) of the brain is involved in mechanisms of homeostatic plasticity. We hypothesized that the ECM, being rich in chondroitin sulfate proteoglycans such as brevican, which are suggested to stabilize synapses by their inhibitory effect on structural plasticity, must be remodelled to allow for structural and molecular changes during conditions of homeostatic plasticity. We found a high abundance of cleaved brevican fragments throughout the hippocampus and cortex and in neuronal cultures, with the strongest labelling in perineuronal nets on parvalbumin-positive interneurons. Using an antibody specific for a brevican fragment cleaved by the matrix metalloprotease ADAMTS4, we identified the enzyme as the main brevican-processing protease. Interestingly, we found ADAMTS4 largely associated with synapses. After inducing homeostatic plasticity in neuronal cell cultures by prolonged network inactivation, we found increased brevican processing at inhibitory as well as excitatory synapses, which is in line with the ADAMTS4 subcellular localization. Thus, the ECM is remodelled in conditions of homeostatic plasticity, which may liberate synapses to allow for a higher degree of structural plasticity.
[Mh] Termos MeSH primário: Encéfalo/fisiologia
Matriz Extracelular/fisiologia
Homeostase/fisiologia
Ácido Hialurônico/metabolismo
Modelos Neurológicos
Plasticidade Neuronal/fisiologia
Sinapses/fisiologia
[Mh] Termos MeSH secundário: Proteínas ADAM/metabolismo
Proteína ADAMTS4
Western Blotting
Encéfalo/metabolismo
Brevicam/metabolismo
Fracionamento Celular
Células HEK293
Seres Humanos
Processamento de Imagem Assistida por Computador
Imuno-Histoquímica
Pró-Colágeno N-Endopeptidase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Brevican); 9004-61-9 (Hyaluronic Acid); EC 3.4.24.- (ADAM Proteins); EC 3.4.24.14 (Procollagen N-Endopeptidase); EC 3.4.24.82 (ADAMTS4 Protein); EC 3.4.24.82 (ADAMTS4 protein, human)
[Em] Mês de entrada:1511
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140917
[St] Status:MEDLINE


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[PMID]:25101296
[Au] Autor:Demircan K; Topcu V; Takigawa T; Akyol S; Yonezawa T; Ozturk G; Ugurcu V; Hasgul R; Yigitoglu MR; Akyol O; McCulloch DR; Hirohata S
[Ad] Endereço:Department of Medical Biology, Turgut Ozal University School of Medicine, 06200 Ankara, Turkey.
[Ti] Título:ADAMTS4 and ADAMTS5 knockout mice are protected from versican but not aggrecan or brevican proteolysis during spinal cord injury.
[So] Source:Biomed Res Int;2014:693746, 2014.
[Is] ISSN:2314-6141
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The chondroitin sulfate proteoglycans (CSPGs) aggrecan, versican, and brevican are large aggregating extracellular matrix molecules that inhibit axonal growth of the mature central nervous system (CNS). ADAMTS proteoglycanases, including ADAMTS4 and ADAMTS5, degrade CSPGs, representing potential targets for ameliorating axonal growth-inhibition by CSPG accumulation after CNS injury. We investigated the proteolysis of CSPGs in mice homozygous for Adamts4 or Adamts5 null alleles after spinal cord injury (SCI). ADAMTS-derived 50-60 kDa aggrecan and 50 kDa brevican fragments were observed in Adamts4-/-, Adamts5-/-, and wt mice but not in the sham-operated group. By contrast Adamts4-/- and Adamts5-/- mice were both protected from versican proteolysis with an ADAMTS-generated 70 kDa versican fragment predominately observed in WT mice. ADAMTS1, ADAMTS9, and ADAMTS15 were detected by Western blot in Adamts4-/- mice' spinal cords after SCI. Immunohistochemistry showed astrocyte accumulation at the injury site. These data indicate that aggrecan and brevican proteolysis is compensated in Adamts4-/- or Adamts5-/- mice by ADAMTS proteoglycanase family members but a threshold of versican proteolysis is sensitive to the loss of a single ADAMTS proteoglycanase during SCI. We show robust ADAMTS activity after SCI and exemplify the requirement for collective proteolysis for effective CSPG clearance during SCI.
[Mh] Termos MeSH primário: Proteínas ADAM/metabolismo
Pró-Colágeno N-Endopeptidase/metabolismo
Proteólise
Traumatismos da Medula Espinal/metabolismo
Versicanas/metabolismo
[Mh] Termos MeSH secundário: Proteínas ADAM/genética
Proteína ADAMTS4
Proteína ADAMTS5
Agrecanas/metabolismo
Animais
Axônios/efeitos dos fármacos
Axônios/metabolismo
Brevicam/metabolismo
Seres Humanos
Camundongos
Camundongos Knockout
Pró-Colágeno N-Endopeptidase/genética
Traumatismos da Medula Espinal/fisiopatologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aggrecans); 0 (Brevican); 126968-45-4 (Versicans); EC 3.4.24.- (ADAM Proteins); EC 3.4.24.- (ADAMTS5 Protein); EC 3.4.24.- (Adamts5 protein, mouse); EC 3.4.24.14 (Procollagen N-Endopeptidase); EC 3.4.24.82 (ADAMTS4 Protein); EC 3.4.24.82 (ADAMTS4 protein, human); EC 3.4.24.82 (Adamts4 protein, mouse)
[Em] Mês de entrada:1504
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140808
[St] Status:MEDLINE
[do] DOI:10.1155/2014/693746


  9 / 109 MEDLINE  
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[PMID]:25052349
[Au] Autor:Dwyer CA; Bi WL; Viapiano MS; Matthews RT
[Ad] Endereço:SUNY Upstate Medical University, Syracuse, NY, USA.
[Ti] Título:Brevican knockdown reduces late-stage glioma tumor aggressiveness.
[So] Source:J Neurooncol;120(1):63-72, 2014 Oct.
[Is] ISSN:1573-7373
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Growing evidence supports the important role of the tumor microenvironment (TME) in cancer biology. A defining aspect of the glioma TME is the unique composition and structure of its extracellular matrix (ECM), which enables tumor cells to overcome the inhibitory barriers of the adult central nervous system (CNS). In this way, the TME plays a role in glioma invasion and the cellular heterogeneity that distinguishes these tumors. Brain Enriched Hyaluronan Binding (BEHAB)/brevican (B/b), is a CNS-specific ECM constituent and is upregulated in the glioma TME. Previous studies have shown B/b exerts a pro-invasive function, suggesting it may represent a target to reduce glioma pathogenesis. Herein, we also provide evidence that B/b expression is enriched in the glioma initiating cell (GIC) niche. We demonstrate that B/b plays roles in the pathological progression, aggressiveness, and lethality of tumors derived from human GICs and traditional glioma cell lines. Interestingly, we found that B/b is not required to maintain the defining phenotypic properties of GICs and thereby acts primarily in late stages of glioma progression. This study suggests that the increased expression of B/b in the TME is a valuable therapeutic target for glioma.
[Mh] Termos MeSH primário: Neoplasias Encefálicas/patologia
Encéfalo/patologia
Brevicam/antagonistas & inibidores
Glioma/patologia
Células-Tronco Neoplásicas/patologia
[Mh] Termos MeSH secundário: Adulto
Animais
Neoplasias Encefálicas/metabolismo
Neoplasias Encefálicas/mortalidade
Brevicam/genética
Brevicam/metabolismo
Diferenciação Celular
Sobrevivência Celular
Matriz Extracelular
Feminino
Glioma/metabolismo
Glioma/mortalidade
Seres Humanos
Células-Tronco Neoplásicas/metabolismo
Prognóstico
RNA Interferente Pequeno/genética
Ratos
Ratos Endogâmicos Lew
Taxa de Sobrevida
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bcan protein, rat); 0 (Brevican); 0 (RNA, Small Interfering)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140724
[St] Status:MEDLINE
[do] DOI:10.1007/s11060-014-1541-z


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[PMID]:24903590
[Au] Autor:Saroja SR; Sase A; Kircher SG; Wan J; Berger J; Höger H; Pollak A; Lubec G
[Ad] Endereço:Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
[Ti] Título:Hippocampal proteoglycans brevican and versican are linked to spatial memory of Sprague-Dawley rats in the morris water maze.
[So] Source:J Neurochem;130(6):797-804, 2014 Sep.
[Is] ISSN:1471-4159
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Proteoglycans (PGs) are major constituents of the extracellular matrix and have recently been proposed to contribute to synaptic plasticity. Hippocampal PGs have not yet been studied or linked to memory. The aim of the study, therefore, was to isolate and characterize rat hippocampal PGs and determine their possible role in spatial memory. PGs were extracted from rat hippocampi by anion-exchange chromatography and analyzed by nano LC-MS/MS. Twenty male Sprague-Dawley rats were tested in the morris water maze. PGs agrin, amyloid beta A4 protein, brevican, glypican-1, neurocan, phosphacan, syndecan-4, and versican were identified in the hippocampi. Brevican and versican levels in the membrane fraction were higher in the trained group, correlating with the time spent in the target quadrant. α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor GluR1 was co-precipitated with brevican and versican. Levels for a receptor complex containing GluR1 was higher in trained while GluR2 and GluR3-containing complex levels were higher in yoked rats. The findings provide information about the PGs present in the rat hippocampus, demonstrating that versican and brevican are linked to memory retrieval in the morris water maze and that PGs interact with α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor GluR1, which is linked to memory retrieval. Proteoglycans (PGs) are major constituents of the extracellular matrix of the brain and were proposed to contribute to synaptic plasticity. This report addressed PGs in rat hippocampus and suggests that PGs brevican and versican are linked to spatial memory, and form a complex with the GluR1 subunit of the AMPA receptor, a key signaling molecule in memory mechanisms.
[Mh] Termos MeSH primário: Brevicam/fisiologia
Hipocampo/metabolismo
Hipocampo/fisiologia
Aprendizagem em Labirinto/fisiologia
Memória/fisiologia
Percepção Espacial/fisiologia
Versicanas/fisiologia
[Mh] Termos MeSH secundário: Animais
Western Blotting
Brevicam/isolamento & purificação
Brevicam/metabolismo
Eletroforese em Gel de Poliacrilamida
Imunoprecipitação
Masculino
Proteínas de Membrana/química
Ratos
Ratos Sprague-Dawley
Receptores de AMPA/metabolismo
Versicanas/isolamento & purificação
Versicanas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Brevican); 0 (Membrane Proteins); 0 (Receptors, AMPA); 0 (glutamate receptor ionotropic, AMPA 1); 0 (glutamate receptor ionotropic, AMPA 2); 0 (glutamate receptor ionotropic, AMPA 3); 126968-45-4 (Versicans)
[Em] Mês de entrada:1410
[Cu] Atualização por classe:140904
[Lr] Data última revisão:
140904
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140607
[St] Status:MEDLINE
[do] DOI:10.1111/jnc.12783



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