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

dc.contributorVelandia Romero, Myriam Lucia
dc.contributorCastellanos Parra, Jaime Eduardo
dc.creatorCamacho Ortega, Sigrid Johanna
dc.date.accessioned2023-03-03T15:15:35Z
dc.date.accessioned2023-06-05T14:54:36Z
dc.date.available2023-03-03T15:15:35Z
dc.date.available2023-06-05T14:54:36Z
dc.date.created2023-03-03T15:15:35Z
dc.date.issued2015
dc.identifierhttp://hdl.handle.net/20.500.12495/10099
dc.identifierinstname: Universidad El Bosque
dc.identifierreponame: Repositorio Institucional Universidad El Bosque
dc.identifierrepourl: https://repositorio.unbosque.edu.co
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/6642560
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.
dc.languagespa
dc.publisherMaestría en Ciencias Básicas Biomédicas
dc.publisherUniversidad El Bosque
dc.publisherFacultad de Medicina
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dc.rightshttp://creativecommons.org/licenses/by-nc-sa/4.0/
dc.rightsAcceso abierto
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttp://purl.org/coar/access_right/c_abf2
dc.rights2015
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International
dc.subjectDENV
dc.subjectExcitotoxicidad
dc.subjectVPA
dc.subjectMK 801
dc.subjectApoptosis
dc.subjectNeurodegeneración
dc.titleEvaluación de la excitotoxicidad por glutamato inducida por el virus dengue neuroadaptado D4MB-6


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