Restraint Stress in Mice Alters Set of 25 miRNAs Which Regulate Stress- and Depression-Related mRNAs

Solich, Joanna; Kuśmider, Maciej; Faron-Górecka, Agata; Pabian, Paulina; Dziedzicka-Wasylewska, Marta

doi:10.3390/ijms21249469

Cited by 10 publications

(11 citation statements)

References 46 publications

(32 reference statements)

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“…In the present study, we examined the differentially expressed miRNA profile in a chronic unpredictable mild stress (CUMS)-induced rat model of depression versus normal controls using a high-throughput microarray. We found that miR-26a-3p, a potential miRNA that is responsible for regulation of mRNA-encoding proteins related to stress and depression (23), showed a significant differential expression within the dentate gyrus (DG) hippocampus of CUMS versus control rats and interacted with the phosphate and tension homology deleted on chromsome ten (PTEN)-phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Complementing these findings, the knock-down of miR-26a-3p in DG regions of control rats accelerated neuronal deterioration and induced depression-like behaviors, whereas an up-regulation of miR-26a-3p within DG regions of CUMS-induced depressed rats rescued neuronal deterioration and depression-like phenotypes.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-26a-3p rescues depression-like behaviors in male rats via preventing hippocampal neuronal anomalies

Li¹,

Fan²,

Wang³

et al. 2021

Journal of Clinical Investigation

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Depression is a neuropsychiatric disease associated with neuronal anomalies within specific brain regions. In the present study, we screened microRNA (miRNA) expression profiles in the dentate gyrus (DG) of hippocampus and found miR-26a-3p was markedly down-regulated in the rat model of depression, whereas up-regulation of miR-26a-3p within DG regions rescued the neuronal deterioration and depression-like phenotypes resulting from stress exposure, effects which appear to be mediated by the PTEN pathway.The knock-down of miR-26a-3p in DG regions of normal control rats induced depressionlike behaviors, effects which were accompanied with an activation of PTEN-PI3K/Akt signaling pathway and neuronal deterioration via suppression of autophagy, impairments in synaptic plasticity and the promotion of neuronal apoptosis. In conclusion, these results suggested that a miR-26a-3p deficits within the hippocampal DG mediated the neuronal anomalies contributing to the display of depression-like behaviors. This miRNA may serve as a potential therapeutic target for the treatment of depression.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-26a-3p rescues depression-like behaviors in male rats via preventing hippocampal neuronal anomalies

Li¹,

Fan²,

Wang³

et al. 2021

Journal of Clinical Investigation

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“…Taken together, these results indicate that lower levels of certain miR-NAs enable an organism to better cope with stress, probably via reduction of the main effect of miRNAs, i.e., the inhibition of translation processes. On the other hand, our previous studies [4,5] showed that the effect of RS was different in the mouse serum, i.e., more miRNAs were downregulated (10) than upregulated (4) in the PFC, while in the serum, the relations were the opposite (15 miRNAs were upregulated vs. 10 that were downregulated). Among these miRNAs were mmu-miR-99a-5p and mmu-miR-23a-3p, which were also detected in the PFC in the present study.…”

Section: Discussionmentioning

confidence: 86%

“…In the previous study, we were able to identify numerous miRNAs that are present in the mouse serum, which differentiated three strains of mice depending on their response to restraint stress (RS) [4,5]. These miRNAs might be regarded as biomarkers of stress resilience.…”

Section: Discussionmentioning

confidence: 99%

“…Three strains of mice with various susceptibility to restraint stress (RS), i.e., mice with a knocked-out gene that encodes the norepinephrine transporter (NET-KO), as well as C57BL/6J (WT) and SWR/J mice, were shown to serve as a good model to study the mechanisms underlying different stress-coping strategies. In our recent study, we were able to show alterations at the level of microRNAs (miRNAs) in the serum of these three genotypes, both between strains and regarding their response to RS [4,5]. MicroRNA molecules present in the blood may serve as potential biomarkers for brain pathologies, including depressive disorders [6,7], but their presence and possible alterations in the specific brain regions are even more interesting.…”

Section: Introductionmentioning

confidence: 99%

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

Solich

Kolasa

Faron-Górecka

et al. 2021

IJMS

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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.

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“…Since they are released by cells and circulate in biological fluids such as blood, microRNAs can easily be measured with a diverse range of robust techniques, such as small RNA sequencing, microarrays, and quantitative polymerase chain reaction (PCR). In recent studies, using three genotypes of mice that were shown to display different sensitivity to restraint stress (RS) [ 40 ], we identified a set of 25 miRNAs altered by RS [ 41 ]. These miRNAs are responsible for regulating mRNAs encoding proteins that are key to the main hypotheses of depression (e.g., monoaminergic receptors and their transporters, neurotrophic factors, neuropeptides and their receptors, glucocorticoid receptors, glutamate and GABA receptors and their transporters, as well as interleukins, TNF, interferon, and their receptors).…”

Section: Microrna As Biomarkers Of Stress Resiliencementioning

confidence: 99%

What Do the Animal Studies of Stress Resilience Teach Us?

Dziedzicka-Wasylewska

Solich

Korlatowicz

et al. 2021

Cells

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Long-lasting stress factors, both biological and psychological, are commonly accepted as the main cause of depressive disorders. Several animal models, using various stressful stimuli, have been used to find biochemical and molecular alterations that could help us understand the etiopathogenesis of depression. However, recent sophisticated studies indicate that the most frequently used animal models of stress only capture a portion of the molecular features associated with complex human disorders. On the other hand, some of these models generate groups of animals resilient to stress. Studies of the mechanisms of stress resilience bring us closer to understanding the process of adapting to aversive stimuli and the differences between stress-susceptible vs. resilient phenotypes. Especially interesting in this context is the chronic mild stress (CMS) experimental paradigm, most often using rats. Studies using this animal model have revealed that biochemical (e.g., the dopamine D2 receptor) and molecular (e.g., microRNA) alterations are dynamic (i.e., depend on stress duration, 2 vs. 7 weeks) and much more pronounced in stress-resilient than stress-susceptible groups of animals. We strongly suggest that studies aimed at understanding the molecular and biochemical mechanisms of depression must consider these dynamics. A good candidate to serve as a biomarker in such studies might be serum microRNA, since it can be obtained relatively easily from living individuals at various time points.

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Restraint Stress in Mice Alters Set of 25 miRNAs Which Regulate Stress- and Depression-Related mRNAs

Cited by 10 publications

References 46 publications

MicroRNA-26a-3p rescues depression-like behaviors in male rats via preventing hippocampal neuronal anomalies

MicroRNA-26a-3p rescues depression-like behaviors in male rats via preventing hippocampal neuronal anomalies

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

What Do the Animal Studies of Stress Resilience Teach Us?

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