MicroRNA Let-7e in the Mouse Prefrontal Cortex Differentiates Restraint-Stress-Resilient Genotypes from Susceptible Genotype

Three strains of mice with various susceptibilities to restraint stress (RS), i.e., mice with a knocked out norepinephrine transporter gene (NET-KO), SWR/J and C57BL/6J (WT) mice were shown to serve as a good model to study the molecular mechanisms underlying different stress-coping strategies. We i...

Full description

Saved in:
Bibliographic Details
Published in:International journal of molecular sciences 2021-08, Vol.22 (17), p.9439
Main Authors: Solich, Joanna, Kolasa, Magdalena, Faron-Górecka, Agata, Hajto, Jacek, Piechota, Marcin, Dziedzicka-Wasylewska, Marta
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
AKT protein
Annotations
Biosynthesis
Coping
Emotional disorders
Forkhead protein
FOXO1 protein
Gene expression
Genotype & phenotype
Genotypes
Histones
MAP kinase
MicroRNAs
miRNA
Molecular modelling
Mood disorders
mRNA
NET-KO mice
Next-generation sequencing
Norepinephrine
Norepinephrine transporter
Physiology
Prefrontal cortex
Resilience
restraint stress
Rodents
stress resilience
SWR/J mice
Thyroid gland
Transcription factors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Three strains of mice with various susceptibilities to restraint stress (RS), i.e., mice with a knocked out norepinephrine transporter gene (NET-KO), SWR/J and C57BL/6J (WT) mice were shown to serve as a good model to study the molecular mechanisms underlying different stress-coping strategies. We identified 14 miRNAs that were altered by RS in the PFC of these mice in a genotype-dependent manner, where the most interesting was let-7e. Further in silico analysis of its potential targets allowed us to identify five mRNAs (Bcl2l11, Foxo1, Pik3r1, Gab1 and Map2k4), and their level alterations were experimentally confirmed. A next-generation sequencing (NGS) approach, which was employed to find transcripts differentially expressed in the PFC of NET-KO and WT mice, showed that, among others, two additional mRNAs were regulated by mmu-let-7e, i.e., mRNAs that encode Kmt2d and Inf2. Since an increase in Bcl2l11 and Pik3r1 mRNAs upon RS in the PFC of WT mice resulted from the decrease in mmu-let-7e and mmu-miR-484 regulations, we postulated that MAPK, FoxO and PI3K-Akt signaling pathways were associated with stress resilience, although via different, genotype-dependent regulation of various mRNAs by let-7e and miR-484. However, a higher level of Kmt2d mRNA (regulated by let-7e) that was found with NGS analysis in the PFC of NET-KO mice indicated that histone methylation was also important for stress resilience.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22179439