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Mecanismos de la acción neuroprotectora de los cannabinoides en la enfermedad de Alzheimer

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  • Indizen technologies

Abstract

El papel neuroprotector de los cannabinoides in vivo e in vitro es conocido, pero el mecanismo a través del cual llevan a cabo su acción neuroprotectora, en el contexto de la enfermedad de Alzheimer, no había sido abordado en su conjunto. Los objetivos del presente trabajo son 5: 1. Estudiar el efecto de distintos agonistas cannabinoides, en particular aquellos carentes de efectos psicoactivos, sobre funciones microgliales tales como la generación de nitritos o la migración, que puedan ser relevantes para la terapia de la EA. 2. Comprobar si el tratamiento prolongado con cannabinoides previene la hipoactividad y los déficits cognitivos que muestran ratones Tg APP y si estos cambios están asociados a una menor activación glial, a una disminución en parámetros inflamatorios ó a niveles de Aβ. 3. Investigar las modificaciones en la expresión y localización de receptores cannabinoides y niveles de sus ligándos endógenos, en el modelo transgénico de la EA y comprobar el efecto del tratamiento prolongado con cannabinoides. 4. Estudiar el metabolismo cerebral in vivo por técnicas de tomografía por emisión de positrones (captación de glucosa) o por espectroscopía de resonancia magnética de protón (niveles relativos de N-acetilaspartato y colina) en ratones Tg APP y el efecto del tratamiento prolongado con cannabinoides. 5. Valorar in vivo mediante técnicas de resonancia magnética de protón (coeficiente de difusión aparente y transferencia de magnetización) si existen cambios cuantificables debidos a la patología tipo EA en el Tg APP y al efecto del tratamiento con cannabinoides.
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