{"id":116407,"date":"2018-03-11T10:45:29","date_gmt":"2018-03-11T10:45:29","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/biochemistry-function-and-pharmacology-of-serotonin-5-ht2a-and-group-ii-metabotropic-glutamate-receptors-in-postmortem-human-brain-interest-for-psychosis\/"},"modified":"2018-03-11T10:45:29","modified_gmt":"2018-03-11T10:45:29","slug":"biochemistry-function-and-pharmacology-of-serotonin-5-ht2a-and-group-ii-metabotropic-glutamate-receptors-in-postmortem-human-brain-interest-for-psychosis","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/farmacos-psicotropicos\/biochemistry-function-and-pharmacology-of-serotonin-5-ht2a-and-group-ii-metabotropic-glutamate-receptors-in-postmortem-human-brain-interest-for-psychosis\/","title":{"rendered":"Biochemistry, function and pharmacology of serotonin 5-ht2a and group ii metabotropic glutamate receptors in postmortem human brain. interest for psychosis"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Mar\u00eda  Patricia Miranda Azpiazu <\/strong><\/h2>\n<p>La esquizofrenia es una enfermedad mental cuya caracter\u00edstica principal es la presencia de sintomatolog\u00eda positiva (habitualmente alucinaciones). El receptor de serotonina 2a (5-ht2ar) es diana farmacol\u00f3gica tanto de drogas alucin\u00f3genas como de antipsic\u00f3ticos at\u00edpicos. Numerosos hallazgos muestran la relevancia de 5-ht2ar en esquizofrenia, habi\u00e9ndose propuesto una sobre expresi\u00f3n e hiperactividad de estos receptores en relaci\u00f3n a la enfermedad. Por otro lado, se ha descrito un d\u00edmero conformado por 5-ht2ar y los receptores metabotr\u00f3picos de glutamato 2 (mglu2rs). La existencia de este heterocomplejo queda establecida en modelos celulares y animales, pero la informaci\u00f3n disponible en humano es limitada. En este contexto, los objetivos principales del presente estudio fueron: i) determinar la expresi\u00f3n g\u00e9nica de 5-ht2ar y mglu2r, y la posible desregulaci\u00f3n de su se\u00f1alizaci\u00f3n mediada por factores de transcripci\u00f3n (egrs) y enzimas relacionadas (hdacs) en cerebro humano postmortem (corteza dorsolateral prefrontal) de sujetos con esquizofrenia y controles, y ii) evaluar el status de se\u00f1alizaci\u00f3n de diferentes agonistas y antagonistas de 5-ht2ar y mglu2r en cerebro humano de controles. Para ello, se emplearon las t\u00e9cnicas de reacci\u00f3n en cadena de la polimerasa (pcr) y ensayos de estimulaci\u00f3n de la fijaci\u00f3n de [35s]gtp\u00c2\u00bfs acoplados a inmunoprecipitaci\u00f3n (spa). Los resultados obtenidos apoyan una reducci\u00f3n de la expresi\u00f3n g\u00e9nica de 5-ht2ar en esquizofrenia debida al tratamiento con antipsic\u00f3ticos at\u00edpicos, confirmada mediante posteriores estudios en animales. Se demuestra una selectividad funcional de agonistas y antagonistas 5-ht2ar en cerebro humano, apoyada en estudios con animales transg\u00e9nicos. Los alucin\u00f3genos no s\u00f3lo inducen la activaci\u00f3n de la v\u00eda can\u00f3nica g\u00c2\u00bfq\/11 al activar 5-ht2ar, sino que en presencia del complejo tambi\u00e9n inducen la activaci\u00f3n de prote\u00ednas g\u00c2\u00bfi\/o. Estos hallazgos sugieren que las propiedades alucin\u00f3genas de los agonistas 5-ht2ar son mediadas fundamentalmente mediante la activaci\u00f3n de las prote\u00ednas inhibitorias g\u00c2\u00bfi1 y g\u00c2\u00bfz, y que esta activaci\u00f3n requiere de la presencia del heterocomplejo. Adem\u00e1s, se demuestra que el agonista mglu2\/3r empleado, ly379268, se\u00f1aliza espec\u00edficamente a trav\u00e9s de mglu2r y no de mglu3r, as\u00ed como que sus acciones son tambi\u00e9n mediadas a trav\u00e9s del receptor de dopamina d2 al activar las prote\u00ednas g\u00c2\u00bfq\/11 y g\u00c2\u00bfz.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Biochemistry, function and pharmacology of serotonin 5-ht2a and group ii metabotropic glutamate receptors in postmortem human brain. interest for psychosis<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Biochemistry, function and pharmacology of serotonin 5-ht2a and group ii metabotropic glutamate receptors in postmortem human brain. interest for psychosis <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Mar\u00eda  Patricia Miranda Azpiazu <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Pa\u00eds vasco\/euskal herriko unibertsitatea<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 30\/09\/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>Jos\u00e9 Javier Meana Martinez<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Juan  Antonio Mic\u00f3 segura <\/li>\n<li>joan Salles alvira (vocal)<\/li>\n<li>Mar\u00eda  adela Sanchez garcia (vocal)<\/li>\n<li>Jos\u00e9 Javier Miguel hidalgo (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Mar\u00eda Patricia Miranda Azpiazu La esquizofrenia es una enfermedad mental cuya caracter\u00edstica principal es la presencia 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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