Diferencias en el estado de la cromatina de astrocitos primarios de corteza de rata inducidos a senescencia o a gliosis con palmitato

Cellular senescence and gliosis in the brain play a crucial role in the development of neurodegenerative diseases and cognitive decline. Factors such as oxidative stress induced by a high-fat diet have been identified as promoters of these phenotypes in the brain. This study aims to identify changes...

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Bibliographic Details
Author: Karla Estephania Ávila Galicia
Format: master thesis
Status:Published version
Publication Date:2024
Country:México
Institution:Universidad Autónoma Metropolitana
Repository:Repositorio Institucional de la UAM Iztapalapa
Language:Spanish
OAI Identifier:oai:bindani.izt.uam.mx:dj52w533c
Online Access:https://doi.org/10.24275/uami.dj52w533c
Access Level:Open access
Keyword:info:eu-repo/classification/LEM/Neuroglia
info:eu-repo/classification/LEM/Cells -- Aging
info:eu-repo/classification/LEM/Células -- Envejecimiento
info:eu-repo/classification/cti/3
Description
Summary:Cellular senescence and gliosis in the brain play a crucial role in the development of neurodegenerative diseases and cognitive decline. Factors such as oxidative stress induced by a high-fat diet have been identified as promoters of these phenotypes in the brain. This study aims to identify changes in epigenetic marks and factors associated with chromatin state modifications in senescent and reactive astrocytes to understand how both cellular phenotypes are regulated at the epigenetic level. To this end, primary cultures of astrocytes were obtained from the cerebral cortex of neonatal rats and exposed to specific concentrations of palmitate, a saturated fatty acid commonly found in high-fat diets, to induce either senescence or gliosis. Epigenetic marks H3K9ac and H3K9me3, the expression of the enzymes Sirt1 and SUV39H1, and other epigenetic factors were then evaluated using immunofluorescence techniques and RNA sequencing (RNA-seq) analysis. The results revealed a significant increase in epigenetic marks in both cellular states. In senescent astrocytes, a higher intensity of the H3K9me3 mark and an increase in SUV39H1 were observed, suggesting the formation of heterochromatin foci. In reactive astrocyte s, a greater number of differentially expressed epigenetic factors were identified compared to senescent astrocytes, mainly associated with transcriptional regulation, chromatin remodeling, and metabolic changes. These findings indicate that while chromatin state changes in reactive astrocytes are regulated, senescent astrocytes appear to lose this control, potentially leading to processes of ex-differentiation.