{"id":99853,"date":"2018-03-11T10:21:05","date_gmt":"2018-03-11T10:21:05","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/defective-myelination-in-mice-lacking-the-lysophosphatidic-acid-receptor-lpa1-newcomer-models-for-demeyelinating-and-neuroinflammatory-diseases\/"},"modified":"2018-03-11T10:21:05","modified_gmt":"2018-03-11T10:21:05","slug":"defective-myelination-in-mice-lacking-the-lysophosphatidic-acid-receptor-lpa1-newcomer-models-for-demeyelinating-and-neuroinflammatory-diseases","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/neuropatologia\/defective-myelination-in-mice-lacking-the-lysophosphatidic-acid-receptor-lpa1-newcomer-models-for-demeyelinating-and-neuroinflammatory-diseases\/","title":{"rendered":"Defective myelination in mice lacking the lysophosphatidic acid receptor lpa1: newcomer models for demeyelinating and neuroinflammatory diseases"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Beatriz Garcia Diaz <\/strong><\/h2>\n<p>T\u00edtulo de la tesis: defective myelination in mice lacking the lysophosphatidic acid receptor lpa1: newcomer modele for demyelinating and neuroinflammatory diseases. el \u00e1cido llsofosfat\u00eddico (lpa) es un fosfol\u00edpido end\u00f3geno que act\u00faa en m\u00faltiples procesos a trav\u00e9s de receptores espec\u00edficos (lpa1-5) acoplados a proteinas-g. A partir de los estudios de los ratones de la variedad m\u00e1laga nulos para lpa1 (malpa1-null), carentes del receptor, se ha demostrado la necesidad del receptor para la proliferaci\u00f3n y diferenciaci\u00f3n de los precursores neurales, tanto durante el desarrollo como en el adulto. La caracterizaci\u00f3n se ha extendido a la glia mielinizante, que expresa espec\u00edficamente lpa1 de manera correlacionada a la m\u00edel\u00edn\u00edzaci\u00f3n, lo que convierte al animal en un modelo interesante para el estudio de patolog\u00edas desmieiinizantes, siendo estos estudios los que constituyen la mayor parte de los resultados de esta tesis. en ausencia de lpa1 los animales muestran d\u00e9ficit cortical de mielina demostrada, principalmente, por la disminuci\u00f3n de expresi\u00f3n de mbp y plp, tanto por  inmunocitoqu\u00edmica como por westem-blot la alteraci\u00f3n de la mielina se confirma por los estudios de microscop\u00eda electr\u00f3nica asi como por los an\u00e1lisis de espectroscopia por resonancia magn\u00e9tica que demuestran un patr\u00f3n de colina afectado. Adem\u00e1s, se ha realizado conteo de la poblaci\u00f3n oligodendrocitar\u00eda por estereolog\u00eda, mostr\u00e1ndose una reducci\u00f3n claramente significativa en ausencia del receptor lpa1. Los resultados demuestran que la ausencia de dicho receptor altera la producci\u00f3n de ol\u00edgodendrocitos en el animal y genera un patr\u00f3n deficitario de mielina, siendo causado, cuanto menos, por alteraciones del transporte intracelular de la prote\u00edna proteolip\u00eddica plp de la mielina. Por otra parte, el lpa regula procesos neurolnflamatorios a trav\u00e9s de lpa1, lpa2 y lpa3 que intervienen en la liberaci\u00f3n de interteucinas, la permeabilizaci\u00f3n de la barrera hematoencef\u00e1lica, as\u00ed como en la activaci\u00f3n de la microgifa. Se ha estudiado el papel del lpa en un modelo neuroinflamatorio y desmielinizante, la encefalomlel\u00edtis autoinmune experimental (eae) a trav\u00e9s de la inmunizaci\u00f3n frente al p\u00e9ptido de mielina mog35-55. La valoraci\u00f3n de la respuesta se ha realizado en ratones normales y carentes de lpa1 atendiendo a par\u00e1metros funcionales e histol\u00f3gicos, demostr\u00e1ndose que es precisa la presencia del receptor para que pueda desarrollarse una respuesta inmune adecuada. En ambos genotipos se manifiesta la patolog\u00eda con curso cl\u00ednico similar, gener\u00e1ndose un patr\u00f3n en brotes con repitencia y recurrencia, los ratones normales mostraron cursos cl\u00ednicos m\u00e1s severos que los nulos para lpa1, existiendo en estos \u00faltimos un rebaso en la aparici\u00f3n de los s\u00edntomas respecto a los normales. Paralelamente los ratones nulos mostraron una mejor recuperaci\u00f3n tras los s\u00edntomas.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Defective myelination in mice lacking the lysophosphatidic acid receptor lpa1: newcomer models for demeyelinating and neuroinflammatory diseases<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Defective myelination in mice lacking the lysophosphatidic acid receptor lpa1: newcomer models for demeyelinating and neuroinflammatory diseases <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Beatriz Garcia Diaz <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 M\u00e1laga<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 19\/03\/2010<\/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>Guillermo Estivill Torr\u00fas<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: carmen Guaza rodriguez <\/li>\n<li>bruno Stankoff (vocal)<\/li>\n<li>pit Stinissen (vocal)<\/li>\n<li>Fernando Rodriguez de fonseca (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Beatriz Garcia Diaz T\u00edtulo de la tesis: defective myelination in mice lacking the lysophosphatidic acid receptor lpa1: 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