Efectos modulatorios del litio sobre la cascada de señalización mediada por fosfoinositoles en cultivo neuronal primario

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dc.contributor.advisorNasi Lignarolo, Enrico
dc.contributor.authorGuevara Espitia, Camilo Andrés
dc.contributor.researchgroupBiofísica de la Señalización Celularspa
dc.date.accessioned2022-03-15T19:47:42Z
dc.date.available2022-03-15T19:47:42Z
dc.date.issued2021
dc.descriptionilustraciones, graficasspa
dc.description.abstractEl litio es el fármaco estándar para el tratamiento del trastorno bipolar. Sin embargo, su mecanismo de acción a nivel celular no está dilucidado. En líneas celulares en nuestro laboratorio se observaron efectos modulatorios del litio sobre respuestas fisiológicas dependientes de la vîa de los fosfoinositoles. Considerando la expresión de distintas isoformas de las proteínas Gq y PLCβ en el sistema nervioso, este trabajo se propuso extender estas observaciones a un primer modelo neuronal. Para ello se utilizaron cultivos primarios de neuronas enzimáticamente disociadas de cerebelo de embrión de pollo. Algunas neuronas fueron identificadas como células de Purkinje y su estimulación con el agonista glutamatérgico quisquilato evocó corrientes de entrada registradas con la técnica de patch clamp e incrementos de calcio intracelular medidos con indicadores fluorescentes de calcio. El rol de la vía de la PLC sobre estas respuestas fue comprobado mostrando su sensibilidad al inhibidor de la PLC U-73122 y la contribución mayoritaria de depósitos intracelulares sobre la movilización de calcio. Finalmente se examinó el efecto del litio sobre las respuestas al quisquilato. En algunas células, exposición aguda a 10mM de litio produjo potenciación de la respuesta mientras que en otras hubo una depresión. Este efecto dual puede ser producto de dos subpoblaciones de neuronas con expresión de diferentes isoformas de la PLCβ. Este trabajo constituye el primer reporte del efecto del litio sobre respuestas asociadas a la vía de la PLC en neuronas primarias de pollo, y abre las puertas para su exploración en otras regiones cerebrales. (Texto tomado de la fuente)spa
dc.description.abstractLithium is the treatment of choice for bipolar disorder. However, its cellular mechanism of action has not been elucidated. Previous work from our laboratory found modulatory effects of lithium on physiological responses dependent on the phosphoinositide signaling pathway in mammalian cell lines. Considering the expression of different isoforms of Gq protein and PLCβ in the nervous system, this work aims to extend these observations into a first neuronal model. To achieve this, primary cultures of enzymatically dissociated neurons from chick embryo cerebellum were developed. Some neurons were identified as Purkinje cells and their stimulation with the glutamatergic agonist quisqualate evoked inward currents recorded with the patch clamp technique and increases in intracellular calcium measured with fluorescent calcium indicators. The role of the PLC pathway on these responses was verified by showing its sensitivity to the PLC inhibitor U-73122 and the main contribution of intracellular compartments on calcium mobilization. Finally, the effect of lithium on the responses evoked by quisqualate was examined. In some cells, acute exposure to 10mM lithium potentiated the response, while in others it was depressed. We suggest that the observed effect is the consequence of two subpopulations of neurons with different expression of PLCβ isoforms. This work constitutes the first report in chick primary neurons of the effect of lithium on the PLC pathway and is a first step for the exploration of this phenomenon in other brain regions.eng
dc.description.degreelevelMaestríaspa
dc.description.degreenameMagíster en Ciencias - Biologíaspa
dc.description.researchareaFisiología Celularspa
dc.format.extent87 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/81226
dc.language.isospaspa
dc.publisherUniversidad Nacional de Colombiaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.departmentDepartamento de Biologíaspa
dc.publisher.facultyFacultad de Cienciasspa
dc.publisher.placeBogotá, Colombiaspa
dc.publisher.programBogotá - Ciencias - Maestría en Ciencias - Biologíaspa
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.licenseAtribución-NoComercial 4.0 Internacionalspa
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/spa
dc.subject.agrovocuriCerebrospa
dc.subject.agrovocuribraineng
dc.subject.ddc610 - Medicina y salud::616 - Enfermedadesspa
dc.subject.proposalLitiospa
dc.subject.proposalCascada de los fosfoinositolesspa
dc.subject.proposalEmbrion de pollospa
dc.subject.proposalNeuronas de Purkinjespa
dc.subject.proposalLithiumeng
dc.subject.proposalPLC-pathwayeng
dc.subject.proposalChick embryoeng
dc.subject.proposalPurkinje Neuronseng
dc.subject.unescoEmbriones animalesspa
dc.titleEfectos modulatorios del litio sobre la cascada de señalización mediada por fosfoinositoles en cultivo neuronal primariospa
dc.title.translatedModulatory effects of lithium on the phosphoinositide signaling cascade in primary neuronal cultureeng
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.professionaldevelopmentEstudiantesspa
dcterms.audience.professionaldevelopmentInvestigadoresspa
dcterms.audience.professionaldevelopmentPúblico generalspa
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2spa

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