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http://hdl.handle.net/10609/102366
Títol: | Temporal Integrative Analysis of mRNA and microRNAs Expression Profiles and Epigenetic Alterations in Female SAMP8, a Model of Age-Related Cognitive Decline |
Autoria: | Cosín-Tomàs, Marta Álvarez López, María Jesús Companys Alemany, Júlia Kaliman, Perla González Castillo, Celia Ortuño Sahagún, Daniel Pallàs, Mercè Griñán Ferré, Christian |
Altres: | Universidad de Guadalajara Universitat Oberta de Catalunya (UOC) Universitat de Barcelona (UB) |
Citació: | Cosín-Tomás, M., Álvarez-López, M.J., Companys-Alemany, J., Kaliman, P., González-Castillo, C., Ortuño-Sahagún, D., Pallàs, M. & Griñán-Ferré, C. (2018). Temporal Integrative Analysis of mRNA and microRNAs Expression Profiles and Epigenetic Alterations in Female SAMP8, a Model of Age-Related Cognitive Decline. Frontiers in Genetics, 9(), 1-23. doi: 10.3389/fgene.2018.00596 |
Resum: | A growing body of research shows that epigenetic mechanisms are critically involved in normal and pathological aging. The Senescence-Accelerated Mouse Prone 8 (SAMP8) can be considered a useful tool to better understand the dynamics of the global epigenetic landscape during the aging process since its phenotype is not fully explained by genetic factors. Here we investigated dysfunctional age-related transcriptional profiles and epigenetic programming enzymes in the hippocampus of 2- and 9-month-old SAMP8 female mice using the Senescent-Accelerated Resistant 1 (SAMR1) mouse strain as control. SAMP8 mice presented 1,062 genes dysregulated at 2 months of age, and 1,033 genes at 9 months, with 92 genes concurrently dysregulated at both ages compared to age-matched SAMR1. SAMP8 mice showed a significant decrease in global DNA methylation (5-mC) at 2 months while hydroxymethylation (5-hmC) levels were increased in SAMP8 mice at 2 and 9 months of age compared to SAMR1. These changes were accompanied by changes in the expression of several enzymes that regulate 5-mC and methylcytosine oxidation. Acetylated H3 and H4 histone levels were significantly diminished in SAMP8 mice at 2-month-old compared to SAMR1 and altered Histone DeACetylase (HDACs) profiles were detected in both young and old SAMP8 mice. We analyzed 84 different mouse miRNAs known to be altered in neurological diseases or involved in neuronal development. Compared with SAMR1, SAMP8 mice showed 28 and 17 miRNAs differentially expressed at 2 and 9 months of age, respectively; 6 of these miRNAs overlapped at both ages. We used several bioinformatic approaches to integrate our data in mRNA:miRNA regulatory networks and functional predictions for young and aged animals. In sum, our study reveals interplay between epigenetic mechanisms and gene networks that seems to be relevant for the progression toward a pathological aging and provides several potential markers and therapeutic candidates for Alzheimer's Disease (AD) and age-related cognitive impairment. |
Paraules clau: | Epigenetics Aging Brain Alzheimer's disease Chromatin-modifying enzymes MicroRNA DNA Methylation Histone acetylation |
DOI: | 10.3389/fgene.2018.00596 |
Tipus de document: | info:eu-repo/semantics/article |
Versió del document: | info:eu-repo/semantics/publishedVersion |
Data de publicació: | 11-des-2018 |
Llicència de publicació: | http://creativecommons.org/licenses/by/3.0 |
Apareix a les col·leccions: | Articles Articles cientÍfics |
Arxius per aquest ítem:
Arxiu | Descripció | Mida | Format | |
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mRNA_female_age.pdf | 3,52 MB | Adobe PDF | Veure/Obrir |
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