Evaluación de la excitotoxicidad por glutamato inducida por el virus dengue neuroadaptado D4MB-6

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dc.contributor.advisorVelandia Romero, Myriam Lucia
dc.contributor.advisorCastellanos Parra, Jaime Eduardo
dc.contributor.authorCamacho Ortega, Sigrid Johanna
dc.date.accessioned2023-03-03T15:15:35Z
dc.date.available2023-03-03T15:15:35Z
dc.date.issued2015
dc.description.abstractEl virus de dengue (DENV), a pesar de ser clasificado como un virus no neurotrópico, induce durante la infección manifestaciones neurológicas como la alteración de la conciencia. Hasta el momento, los signos y síntomas neurológicos que aparecen durante la infección por DENV no se han asociado a un mecanismo en particular. Durante la infección con el JEV, WNV y el HIV se produce la disfunción y muerte de neuronas mediada por procesos excitatorios. Para Dengue, hasta el momento sólo se ha reportado en modelos in vivo e in vitro y en muestras post-mortem el daño del tejido y la perdida neuronal, sin embargo no se conoce si durante la infección con este virus suceden eventos excitotoxicos o si la la exacerbada respuesta inmune afecta la superviviencia neuronal En el presente estudio se planteó -utilizando el modelo de neuroinfección desarollado en nuestro laboratorio-, evaluar las posibles causas de alteración y muerte neuronal inducidas por la cepa D4MB-6 y el efecto de dos fármacos, ácido valproico (VPA) y MK-801 con el fin de. Para esto, se infectaron ratones Balb/C de 7 dpn con el D4MB-6 tratados o no tratados con VPA o MK 801. Los animales fueron observados y pesados diariamente por 3 o 6 dpi y sacrificados para la extracción del encéfalo y médula. De estos tejidos se obtuvieron homogenizados o cortes histológicos para evaluar la infección y producción viral, la morfología, la expresión de algunas proteínas pro y anti-apoptóticos. En los animales infectados no tratados, las manifestaciones clínicas fueron evidentes al 3er dpi y severas al 6to dpi, al igual que las alteraciones histológicas, caracterizadas por apoptosis, necrosis y espongiosis neuronal acompañadas de alteraciones vasculares como hemorragias, edema e infiltrado de células mononucleares. En esta misma, condición se observó astrogliosis, neurodegeneración y aumento en la expresión de proteínas pro-apoptóticas, como Casp 3, 8, y Bax. Por el contrario, en los animales infectados y tratados todas las manifestaciones y alteraciones neurológicas fueron reducidas, detectando sólo algunas células en apoptosis y neurodegeneración en el cerebelo de animales infectados y tratados con VPA y MK 801, al igual que la producción y transcritos pro- apoptóticos. Estos resultados sugieren que el virus D4MB-6 induce encefalitis y mielitis, como alteración vascular, así como muerte neuronal mediada por procesos excitotóxicos e inmunológicos. Dichas alteraciones son prevenidas de forma total o parcial con los fármacos MK 801 y VPA.spa
dc.description.abstractenglishThe dengue virus (DENV), despite being classified as a non-neurotropic virus during infection induces neurological symptoms such as impaired consciousness. So far, the neurological signs and symptoms that appear during DENV infection have not been associated to a particular mechanism. During infection with JEV, WNV and HIV dysfunction and neuronal death mediated excitatory process occurs. Dengue, so far only been reported in in vivo and in vitro models and samples postmortem tissue damage and neuronal loss, however not known whether during infection with this virus occur excitotoxic events or the exacerbated immune response affects neuronal survival. In the present study it raised -using neuroinfection model developed in our laboratory-, so evaluate potential causes of impairment and neuronal death induced D4MB-6 strain and the effect of two drugs, valproic acid (VPA) and MK 801. For this, Balb/C mice were infected with D4MB-6 treated or not treated with VPA or MK 801. The animals were observed and weighed daily for 3 or 6 dpi and sacrificed for the removal of the brain and spinal cord. These tissues homogenates or tissue sections to assess viral infection and production, morphology, expression of some pro and anti-apoptotic proteins were obtained. In infected untreated animals, the clinical manifestations were evident to 3rd and severe to the 6th dpi, as well as histological alterations, characterized by apoptosis, neuronal necrosis and spongiosis accompanied by vascular disorders such as bleeding, edema and infiltration of mononuclear cells. In the same, astrogliosis condition, neurodegeneration and increased expression of pro-apoptotic proteins such as Casp3, 8, and Bax it was observed. Conversely, infected and treated at all manifestations and neurological disorders animals were reduced by detecting only a few cells in apoptosis and neurodegeneration in the cerebellum of infected and treated with VPA and MK 801 animals, as the production and transcribed pro- apoptotic. These results suggest that the D4MB-6 virus induces encephalitis and myelitis, and vascular changes and mediated excitotoxic neuronal death and immunological processes. Such alterations are prevented in whole or in part with the MK 801 and VPA drug.eng
dc.description.degreelevelMaestríaspa
dc.description.degreenameMagíster en Ciencias Básicas Biomédicasspa
dc.format.mimetypeapplication/pdf
dc.identifier.instnameinstname:Universidad El Bosquespa
dc.identifier.reponamereponame:Repositorio Institucional Universidad El Bosquespa
dc.identifier.repourlrepourl:https://repositorio.unbosque.edu.co
dc.identifier.urihttps://hdl.handle.net/20.500.12495/10099
dc.language.isospa
dc.publisher.facultyFacultad de Medicinaspa
dc.publisher.grantorUniversidad El Bosquespa
dc.publisher.programMaestría en Ciencias Básicas Biomédicasspa
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dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.accessrightshttps://purl.org/coar/access_right/c_abf2
dc.rights.creativecommons2015
dc.rights.localAcceso abiertospa
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectDENVspa
dc.subjectExcitotoxicidadspa
dc.subjectVPAspa
dc.subjectMK 801spa
dc.subjectApoptosisspa
dc.subjectNeurodegeneraciónspa
dc.subject.keywordsDENVspa
dc.subject.keywordsExcitotoxicityspa
dc.subject.keywordsVPAspa
dc.subject.keywordsMK 801spa
dc.subject.keywordsApoptosisspa
dc.subject.keywordsNeurodegenerationspa
dc.subject.nlmW 50
dc.titleEvaluación de la excitotoxicidad por glutamato inducida por el virus dengue neuroadaptado D4MB-6spa
dc.title.translatedEvaluation of glutamate excitotoxicity induced by dengue virus neuroadapted D4MB -6spa
dc.type.coarhttps://purl.org/coar/resource_type/c_bdcc
dc.type.coarversionhttps://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.driverinfo:eu-repo/semantics/masterThesis
dc.type.hasversioninfo:eu-repo/semantics/acceptedVersion
dc.type.localTesis/Trabajo de grado - Monografía - Maestríaspa

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Maestría en Ciencias Básicas Biomédicas