Please use this identifier to cite or link to this item:

http://hdl.handle.net/10609/102366
Title: Temporal Integrative Analysis of mRNA and microRNAs Expression Profiles and Epigenetic Alterations in Female SAMP8, a Model of Age-Related Cognitive Decline
Author: Cosín Tomás, Marta
Álvarez López, María Jesús
Companys Alemany, Júlia
Kaliman, Perla
González Castillo, Celia
Ortuño Sahagún, Daniel
Pallàs, Mercè
Griñán Ferré, Christian
Keywords: Epigenetics
Aging
Brain
Alzheimer's disease
Chromatin-modifying enzymes
MicroRNA
DNA
Methylation
Histone acetylation
Issue Date: 11-Dec-2018
Publisher: Frontiers in Genetics
Citation: 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
Also see: https://www.frontiersin.org/articles/10.3389/fgene.2018.00596/pdf
Abstract: 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.
Language: English
URI: http://hdl.handle.net/10609/102366
ISSN: 1664-8021MIAR
Appears in Collections:Articles
Articles

Share:
Export:
Files in This Item:
File SizeFormat 
mRNA_female_age.pdf3.52 MBAdobe PDFView/Open

Items in repository are protected by copyright, with all rights reserved, unless otherwise indicated.