{"id":116572,"date":"2018-03-11T10:45:46","date_gmt":"2018-03-11T10:45:46","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/degeneracion-de-neuronas-dopaminergicas-de-la-sustancia-negra-de-primates-no-humanos-mediante-la-sobreexpresion-de-lrrk2-g2019s\/"},"modified":"2018-03-11T10:45:46","modified_gmt":"2018-03-11T10:45:46","slug":"degeneracion-de-neuronas-dopaminergicas-de-la-sustancia-negra-de-primates-no-humanos-mediante-la-sobreexpresion-de-lrrk2-g2019s","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/ciencias-medicas\/degeneracion-de-neuronas-dopaminergicas-de-la-sustancia-negra-de-primates-no-humanos-mediante-la-sobreexpresion-de-lrrk2-g2019s\/","title":{"rendered":"Degeneraci\u00f3n de neuronas dopamin\u00e9rgicas de la sustancia negra de primates no humanos mediante la sobreexpresi\u00f3n de lrrk2-g2019s"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Carla Gisela Di Caudo <\/strong><\/h2>\n<p>La mutaci\u00f3n de lrrk2 es la m\u00e1s frecuentemente encontrada en la enfermedad de parkinson familiar y espor\u00e1dica. Se utiliz\u00f3 un adenovirus canino como vector de transferencia g\u00e9nica (cav2) con el objetivo de estudiar si la sobreexpresi\u00f3n de lrrk2-g2019s en el primate produce degeneraci\u00f3n de neuronas dopamin\u00e9rgicas de la sustancia negra (sn). Se utilizaron 20 primates de la especia macaca fascicularis.  Los grupos gp1 y gp2 fueron inyectados en putamen y sn con el vector cav2-gfp confirmando el neurotropismo y transporte axonal retr\u00f3grado de cav2. El grupo ge1 fue inyectado con el vector hd-cav2-lrrk2-g2019s en el putamen izquierdo y sacrificado 6 meses despu\u00e9s. Se observaron leves s\u00edntomas motores transitorios y  en los estudios de pet reducci\u00f3n del 20% en la captaci\u00f3n de 11c-dtbz a nivel estriatal que progres\u00f3 al 35% a nivel del putamen posterior a los 6 meses. El n\u00famero de neuronas dopamin\u00e9rgicas de la sn se redujo en 25-35%. Los grupos ge2 y ge3 se inyectaron en la sn izquierda con hd-cav2-gfp o hd-cav2-lrrk2-g2019s y no mostraron cambios significativos  en comportamiento o pet 12 meses despu\u00e9s de la cirug\u00eda.  Sin embargo, las neuronas de la sn de los grupos inyectados con hd-cav2-lrrk2-g2019s presentaron alteraciones morfol\u00f3gicas: presencia de neuritas distr\u00f3ficas e incremento en la concentraci\u00f3n de mitocondrias a nivel del soma. Acompa\u00f1ados de  gliosis reactiva, microgl\u00eda activada e incremento en la fosforilaci\u00f3n p-tau. En resumen, la expresi\u00f3n de lrrk2-g2019s en el cerebro de primates produce disfunci\u00f3n del sistema dopamin\u00e9rgico nigroestriatal y cambios histol\u00f3gicos sugestivos de un estadio inicial de neurodegeneraci\u00f3n.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Degeneraci\u00f3n de neuronas dopamin\u00e9rgicas de la sustancia negra de primates no humanos mediante la sobreexpresi\u00f3n de lrrk2-g2019s<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Degeneraci\u00f3n de neuronas dopamin\u00e9rgicas de la sustancia negra de primates no humanos mediante la sobreexpresi\u00f3n de lrrk2-g2019s <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Carla Gisela Di Caudo <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Navarra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 31\/10\/2014<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>M\u00aa Rosario Luquin Piudo<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: isidro Ferrer abizanda <\/li>\n<li>rosario Sanchez pernaute (vocal)<\/li>\n<li>Jos\u00e9 Luis Lanciego perez (vocal)<\/li>\n<li>eduardo Tolosa sarr\u00f3 (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Carla Gisela Di Caudo La mutaci\u00f3n de lrrk2 es la m\u00e1s frecuentemente encontrada en la enfermedad de [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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