Dynamiques du transcriptome et du protéome au cours du vieillissement dans le cortex frontal de souris
Year: 2022
Type: dissertation
Abstract: Aging is characterized by the accumulation of physiological changes over time that lead to a decline in cell and tissue function. The brain is one of the organs that ages the fastest and its aging is the first risk factor for many neurodegenerative diseases. The frontal cortex (FC) is a cell layer responsible for many cognitive functions, such as planning, memory, and logical decision-making. At the cellular level, FC aging alters many cellular components such as mRNA and protein levels. The aim of this research is to study the dynamics of transcriptome (mRNA) and proteome (proteins) during aging in mouse FC. Our hypothesis is that during aging, there are two groups of genes that show different types of dysregulation: i) transcriptional dysregulation, with a modification of the level of mRNA correlated with that of proteins, and ii) post -transcriptional where RNA dynamics are not reflected in protein levels. The objective is to test which type(s) of dysregulation exist during the aging of the FC. Mouse FC tissues were collected from 6- and 24-month-old mice. RNA sequencing was performed to establish gene expression profiling and assess transcriptomic differences in aging FC. We observed an increase in the expression of genes (n=399) related to immune functions and a decrease in the expression of genes (n=27) related to neuronal functions. By mass spectrometry, we have also characterized the changes in protein abundance during aging. We were not able to confirm the enrichment of proteins with immune functions, probably because the presence of these cells is a minority in the tissue and their detection is more difficult. Therefore, this transcriptional dysregulation, which seems to affect immune cells, remains to be validated by other methodologies, but suggests that it may be at the origin of the neuroinflammation linked to aging in the brain. However, we identified and quantified many proteins whose abundance changes in aging CF. We showed that the RNAs coding for these proteins remain stable during aging, suggesting that a post-transcriptional dysregulation is well established during aging in FC. This loss of proteostasis affects many proteins with neuronal functions, the abnormal abundance of which could be the cause of cognitive decline linked to brain aging. In conclusion, the cross-use of two -omics techniques has highlighted two types of dysregulation that could be the target of new therapeutic strategies by targeting either the RNAs or the proteins affected in the FC during aging.
Author: Khatir, Inès
Institution: Université de Sherbrooke
Language: English
Subfield: Aging
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7201925159