Identificación de genes asociados a cambios neurocomportamentales por la infección con virus Zika en ratones BALB/c

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dc.contributor.advisorÁlvarez Diaz, Diego Alejandrospa
dc.contributor.advisorLozano Moreno, José Manuelspa
dc.contributor.authorChivatá Avila, Jaime Alexanderspa
dc.contributor.cvlacChivatá Avila, Jaime Alexander [0001692043]spa
dc.contributor.researchgroupGenómica de Microorganismos Emergentesspa
dc.date.accessioned2024-07-16T21:18:41Z
dc.date.available2024-07-16T21:18:41Z
dc.date.issued2024-01
dc.descriptionilustraciones (algunas a color), diagramasspa
dc.description.abstractEl virus Zika (ZIKV) es un arbovirus causante del “Síndrome de zika congénito”, asociado con diversos desórdenes del neurodesarrollo (NDDs) donde la microcefalia es una de las manifestaciones más severas. Existen NDDs más leves que pueden pasar desapercibidos en neonatos, como trastornos del espectro autista, retrasos en el desarrollo neuropsicomotor y del lenguaje que resultan en dificultades sociales y académicas. Los modelos murinos de infección por ZIKV reproducen defectos motores y cognitivos reportados en humanos los cuales pueden evaluarse mediante dispositivos comportamentales para su posterior contraste con perfiles de expresión genética, útiles en la caracterización de NDDs por ZIKV. Este estudio se enfocó en identificar genes asociados a cambios comportamentales por la infección con virus Zika en ratones BALB/c juveniles. Se inocularon por vía subcutánea con ZIKV (MH544701.2) ratones con dosis de 6.8x103 PFU al 1 día post-natal (DPN). La presencia del virus en cerebelo y corteza se verificó y cuantificó a los 10 y 30 días post-nfección (DPI) mediante RT-qPCR, los potenciales déficits neuroconductuales se evaluaron a los 30 DPI mediante las pruebas de laberinto en T, rotarod y campo abierto para posteriormente secuenciar y obtener listas genes diferencialmente expresados (DEG) así como categorías funcionales mediante análisis de enriquecimiento de conjunto de genes (GSEA). Se obtuvo un modelo de infección por ZIKV con capacidad de infectar para infectar cerebro, permitir la sobrevida más allá del 30 DPI y causar alteraciones comportamentales leves relacionadas con la actividad cognitiva, pero no con la motora o motivacional, asociada a una fuerte subregulación de genes relacionados con la sinapsis y con funciones estructurales en axones, dendritas y recubrimiento de mielina. En conjunto, estos datos proporcionan nueva información sobre los genes y las posibles vías moleculares que se ven alteradas en un proceso de infección leve y sugiere genes candidatos para futuras investigaciones. (Texto tomado de la fuente)spa
dc.description.abstractThe Zika virus (ZIKV) is an arbovirus responsible for the "Congenital Zika Syndrome," associated with various neurodevelopmental disorders (NDDs), where microcephaly is one of the most severe manifestations. Milder NDDs, including autism spectrum disorders and delays in neuropsychomotor and language development, may go unnoticed in neonates, resulting in social and academic challenges. Murine models of ZIKV infection replicate motor and cognitive defects reported in humans, assessable through behavioural devices for subsequent comparison with gene expression profiles, valuable in characterizing ZIKV-induced NDDs. This study aimed to identify genes associated with behavioral changes in Zika virus infection in juvenile BALB/c mice. Mice were subcutaneously inoculated with ZIKV (MH544701.2) at 1 day postnatal (DPN) with a dose of 6.8x103 PFU. Virus presence in cerebellum and cortex was verified and quantified at 10 and 30 days post-infection (DPI) using RT-qPCR. Potential neurobehavioral deficits were evaluated at 30 DPI through T-maze, rotarod, and open-field tests, followed by sequencing to obtain lists of differentially expressed genes (DEGs) and functional categories through gene set enrichment analysis (GSEA). A ZIKV infection model was established with the ability to infect the brain, allow survival beyond 30 DPI, and induce mild behavioral alterations related to cognitive activity but not motor or motivational aspects. This was associated with a strong downregulation of genes related to synapses and structural functions in axons, dendrites, and myelin sheaths. Overall, these data provide new insights into genes and potential molecular pathways altered in a mild infection process, suggesting candidate genes for future investigations. (Texto tomado de la fuente)eng
dc.description.degreelevelMaestríaspa
dc.description.degreenameMagíster en Ciencias - Bioquímicaspa
dc.description.researchareaBiología celular y patogénesis de los agentes emergentes y reemergentes causantes de enfermedades transmisibles.spa
dc.format.extent89 páginasspa
dc.format.mimetypeapplication/pdfspa
dc.identifier.instnameUniversidad Nacional de Colombiaspa
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombiaspa
dc.identifier.repourlhttps://repositorio.unal.edu.co/spa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/86491
dc.language.isospaspa
dc.publisherUniversidad Nacional de Colombiaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.facultyFacultad de Cienciasspa
dc.publisher.placeBogotá, Colombiaspa
dc.publisher.programBogotá - Ciencias - Maestría en Ciencias - Bioquímicaspa
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.licenseAtribución-NoComercial-SinDerivadas 4.0 Internacionalspa
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/spa
dc.subject.ddc540 - Química y ciencias afinesspa
dc.subject.decsTrastornos del neurodesarrollospa
dc.subject.decsNeurodevelopmental disorderseng
dc.subject.decsNeurociencia cognitivaspa
dc.subject.decsCognitive neuroscienceeng
dc.subject.decsInfección por el virus Zikaspa
dc.subject.decsZika virus infectioneng
dc.subject.lembVirus del tumor murinospa
dc.subject.lembMouse mammary tumor viruseng
dc.subject.proposalModelo de infecciónspa
dc.subject.proposaldesordenes del neurodesarrollo (NDDs)spa
dc.subject.proposalExpresión diferencialspa
dc.subject.proposalEnriquecimiento funcionalspa
dc.subject.proposalTranscriptómicaspa
dc.subject.proposalInfection modeleng
dc.subject.proposalNeurodevelopmental disorders (NDDs)eng
dc.subject.proposalDifferential expressioneng
dc.subject.proposalFunctional enrichmenteng
dc.subject.proposalTranscriptomicseng
dc.subject.wikidataTranscriptómicaspa
dc.subject.wikidataTranscriptomeeng
dc.titleIdentificación de genes asociados a cambios neurocomportamentales por la infección con virus Zika en ratones BALB/cspa
dc.title.translatedIdentification of genes associated with neurobehavioral changes due to zika virus infection in BALB/c miceeng
dc.typeTrabajo de grado - Maestríaspa
dc.type.coarhttp://purl.org/coar/resource_type/c_bdccspa
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aaspa
dc.type.contentTextspa
dc.type.driverinfo:eu-repo/semantics/masterThesisspa
dc.type.redcolhttp://purl.org/redcol/resource_type/TMspa
dc.type.versioninfo:eu-repo/semantics/acceptedVersionspa
dcterms.audience.professionaldevelopmentInvestigadoresspa
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2spa
oaire.fundernameInstituto Nacional de Saludspa

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Maestría en Ciencias - Bioquímica