Análisis de la modificación epigenética H3K9me2 en el hipocampo de un modelo de la enfermedad de Alzheimer
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Fecha
2020
Profesor/a Guía
Facultad/escuela
Idioma
es
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Universidad Andrés Bello
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Licencia CC
Licencia CC
Resumen
La enfermedad de Alzheimer (EA) posee tres características que en
conjunto la distinguen de otras neuropatologías: presencia de ovillos
neurofibrilares intracelulares, placas seniles en hipocampo y corteza, y déficit
cognitivo. Estudios en modelos en la EA sugieren la presencia de alteraciones
epigenéticas, particularmente en la metilación de histonas, que llevarían a la
descondensación de la cromatina induciendo la expresión aberrante de genes.
En base a esto, hipotetizamos que, en el hipocampo del modelo murino de la
EA APPSwe/PSEN1ΔE9, hay una disminución en la dimetilación de la lisina 9
de la histona 3 (H3K9me2), una modificación post-traduccional de histonas, que
reprime la transcripción génica. Para evaluar esto, analizamos los niveles
globales de H3K9me2 mediante western blot en extractos nucleares de
hipocampo del modelo APPSwe/PSEN1ΔE9 en estados avanzados de la EA.
Además, evaluamos por inmunofluorescencia los niveles de H3K9me2 en giro
dentado, CA1 y CA3 del hipocampo del modelo APPSwe/PSEN1ΔE9. Los
resultados obtenidos demuestran que hay una disminución en los niveles de la
modificación represiva H3K9me2 en el hipocampo del modelo murino de EA, lo
que podría estar asociado a la desregulación génica previamente descrita en la
patología
Alzheimer's disease (AD) has three classical hallmarks that distinguish it from other neuropathologies: the presence of intracellular neurofibrillary tangles, senile plaques in the hippocampus and cortex, and cognitive deficits. Studies in AD models suggest epigenetic alterations in the disease, particularly in histone methylation that would lead to chromatin decondensation, inducing aberrant gene expression. Based on that, we hypothesize that in the hippocampus of the mouse model of AD, APPSwe/PSEN1ΔE9, there is a decrease in the dimethylation of lysine 9 on histone H3 (H3K9me2), a histone post-translational modification that represses gene transcription. To evaluate this, we analyzed the global levels of H3K9me2 by western blot in nuclear extracts from total hippocampus of the mouse model APPSwe/PSEN1ΔE9, at advanced stages of AD. In addition, we evaluated the level of H3K9me2 in the dentate gyrus CA1 and CA3 regions of the hippocampus by immunofluorescence. The results obtained show that there is a decrease in the levels of the repressive modification H3K9me2 in the hippocampus of the murine model for Alzheimer’s disease, which could be associated with the previously described deregulation of gene expression in the pathology.
Alzheimer's disease (AD) has three classical hallmarks that distinguish it from other neuropathologies: the presence of intracellular neurofibrillary tangles, senile plaques in the hippocampus and cortex, and cognitive deficits. Studies in AD models suggest epigenetic alterations in the disease, particularly in histone methylation that would lead to chromatin decondensation, inducing aberrant gene expression. Based on that, we hypothesize that in the hippocampus of the mouse model of AD, APPSwe/PSEN1ΔE9, there is a decrease in the dimethylation of lysine 9 on histone H3 (H3K9me2), a histone post-translational modification that represses gene transcription. To evaluate this, we analyzed the global levels of H3K9me2 by western blot in nuclear extracts from total hippocampus of the mouse model APPSwe/PSEN1ΔE9, at advanced stages of AD. In addition, we evaluated the level of H3K9me2 in the dentate gyrus CA1 and CA3 regions of the hippocampus by immunofluorescence. The results obtained show that there is a decrease in the levels of the repressive modification H3K9me2 in the hippocampus of the murine model for Alzheimer’s disease, which could be associated with the previously described deregulation of gene expression in the pathology.
Notas
Tesis (Licenciado en Biología)
Palabras clave
Enfermedad de Alzheimer, Epigénesis Genética