Hippocampal MicroRNAs Respond to Administration of Antidepressant Fluoxetine in Adult Mice

Miao, Nan; Jin, Junghee; Kim, Seung-Nam; Sun, Tao

doi:10.3390/ijms19030671

Cited by 15 publications

(14 citation statements)

References 66 publications

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“…These results in part suggest that antidepressant treatment does not totally reverse chronic stress pathology, but rather cause novel alteration. Similar to our study, Miao N [38] found enrichment of target antidepressant-altered miRNA in axon guidance pathways, emphasizing roles of this pathway in antidepressant therapy.…”

Section: Discussionsupporting

confidence: 90%

“…As we can see, only a quarter of treatment-related DE-miRNAs (2/8) overlaps with depressed-related DE-miRNAs. Consistent with this idea, Zhou M [37] studied the miRNA alteration in rats hippocampus caused by CUMS, whereas Miao N [38] and Yang X [39] studied alteration caused by Fluoxetine/Ketamine in the same region, and their results have little overlap. Pan B [40] carried out a similar study with Duloxetine, and the little converging result is found despite miR-124, a well-studied miRNA involved in depression [41] and antidepressant treatment [42].…”

Section: Discussionmentioning

confidence: 97%

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Expression alteration of microRNAs in Nucleus Accumbens is associated with chronic stress and antidepressant treatment in rats

Song

Shen

Zhang

et al. 2019

BMC Med Inform Decis Mak

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BackgroundNucleus Accumbens (NAc) is a vital brain region for the process of reward and stress, whereas microRNA plays a crucial role in depression pathology. However, the abnormality of NAc miRNA expression during the stress-induced depression and antidepressant treatment, as well as its biological significance, are still unknown.MethodsWe performed the small RNA-sequencing in NAc of rats from three groups: control, chronic unpredictable mild stress (CUMS), and CUMS with an antidepressant, Escitalopram. We applied an integrative pipeline for analyzing the miRNA expression alternation in different model groups, including differential expression analysis, co-expression analysis, as well as a subsequent pathway/network analysis to discover both miRNA alteration pattern and its biological significance.ResultA total of 423 miRNAs were included in analysis.18/8 differential expressing (DE) miRNA (adjusted p < 0.05, |log2FC| > 1) were observed in controls Vs. depression/depression Vs. treatment, 2 of which are overlapping. 78% (14/18) of these miRNAs showed opposite trends of alteration in stress and treatment. Two micro RNA, miR-10b-5p and miR-214-3p, appeared to be hubs in the regulation networks and also among the top findings in both differential analyses. Using co-expression analysis, we found a functional module that strongly correlated with stress (R = 0.96, P = 0.003), and another functional module with a moderate correlation with anhedonia (R = 0.89, P = 0.02). We also found that predicted targets of these miRNAs were significantly enriched in the Ras signaling pathway, which is associated with both depression, anhedonia, and antidepressant treatment.ConclusionEscitalopram treatment can significantly reverse NAc miRNA abnormality induced by chronic stress. However, the novel miRNA alteration that is absent in stress pathology also emerges, which means that antidepressant treatment is unlikely to bring miRNA expression back to the same level as the controls. Also, the Ras-signaling pathway may be involved in explaining the depression disease etiology, the clinical symptom, and treatment response of stress-induced depression.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 97%

Expression alteration of microRNAs in Nucleus Accumbens is associated with chronic stress and antidepressant treatment in rats

Song

Shen

Zhang

et al. 2019

BMC Med Inform Decis Mak

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“…Our results are consistent with previous studies that report an upregulation of miR-26a after antidepressant treatments in different brain regions, including the dorsal raphe nuclei, while knocking it down increased anxiety [20]. Another study showed that a fluoxetine treatment increased miR-26b levels in mice hippocampi, while miR-26a showed a nonsignificant increase [55]. MiR-26a and miR-26b were also increased in the blood of depressed patients undergoing treatment with the antidepressant escitalopram [21].…”

Section: Repetitive Stress and Mir-26asupporting

confidence: 92%

A Role for mir-26a in Stress: A Potential sEV Biomarker and Modulator of Excitatory Neurotransmission

Lafourcade

Fernández

Ramírez

et al. 2020

Cells

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Stress is a widespread problem in today’s societies, having important consequences on brain function. Among the plethora of mechanisms involved in the stress response at the molecular level, the role of microRNAs (miRNAs) is beginning to be recognized. The control of gene expression by these noncoding RNAs makes them essential regulators of neuronal and synaptic physiology, and alterations in their levels have been associated with pathological conditions and mental disorders. In particular, the excitatory (i.e., glutamate-mediated) neurotransmission is importantly affected by stress. Here, we found that loss of miR-26a-5p (miR-26a henceforth) function in primary hippocampal neurons increased the frequency and amplitude of miniature excitatory currents, as well as the expression levels of the excitatory postsynaptic scaffolding protein PSD95. Incubation of primary hippocampal neurons with corticosterone downregulated miR-26a, an effect that mirrored our in vivo results, as miR-26a was downregulated in the hippocampus as well as in blood serum-derived small extracellular vesicles (sEVs) of rats exposed to two different stress paradigms by movement restriction (i.e., stress by restraint in cages or by complete immobilization in bags). Overall, these results suggest that miR-26a may be involved in the generalized stress response and that a stress-induced downregulation of miR-26a could have long-term effects on glutamate neurotransmission.

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“…Peng et al indicated that miR-346-5p regulates Wnt/ β -catenin signaling to reduce the expression of downstream genes including c-Myc, CyclinD1, LEF-1, and TCF-1 and subsequent osteogenic differentiation of BMSCs [ 12 ]. Miao et al found that miR-346-5p regulates the differentiation and proliferation of neuronal stem cells by regulating KLF4 expression [ 13 ]. However, the function of miR-346-5p in osteogenic differentiation of BMSCs is still not clear.…”

Section: Introductionmentioning

confidence: 99%

[Retracted] MicroRNA‐346‐5p Regulates Differentiation of Bone Marrow‐Derived Mesenchymal Stem Cells by Inhibiting Transmembrane Protein 9

Zhang

Sun

Liu

et al. 2020

BioMed Research International

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The molecular mechanisms how bone marrow-derived mesenchymal stem cells (BMSCs) differentiate into osteoblast need to be investigated. MicroRNAs (miRNAs) contribute to the osteogenic differentiation of BMSCs. However, the effect of miR-346-5p on osteogenic differentiation of BMSCs is not clear. This study is aimed at elucidating the underlying mechanism by which miR-346-5p regulates osteogenic differentiation of human BMSCs. Results of alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining indicated that upregulation of miR-346-5p suppressed osteogenic differentiation of BMSCs, whereas downregulation of miR-346-5p enhanced this process. The protein levels of the osteoblastic markers Osterix and Runt-related transcription factor 2 (Runx2) were decreased in cells treated with miR-346-5p mimic at day 7 and day 14 after being differentiated. By contrast, downregulation of miR-346-5p elevated the protein levels of Osterix and Runx2. Moreover, a dual-luciferase reporter assay revealed that Transmembrane Protein 9 (TMEM9) was a target of miR-346-5p. In addition, the Western Blot results demonstrated that the TMEM9 protein level was significantly reduced by the miR-346-5p mimic whereas downregulation of miR-346-5p improved the protein level of TMEM9. These results together demonstrated that miR-346-5p served a key role in BMSC osteogenic differentiation of through targeting TMEM9, which may provide a novel target for clinical treatments of bone injury.

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Hippocampal MicroRNAs Respond to Administration of Antidepressant Fluoxetine in Adult Mice

Cited by 15 publications

References 66 publications

Expression alteration of microRNAs in Nucleus Accumbens is associated with chronic stress and antidepressant treatment in rats

Expression alteration of microRNAs in Nucleus Accumbens is associated with chronic stress and antidepressant treatment in rats

A Role for mir-26a in Stress: A Potential sEV Biomarker and Modulator of Excitatory Neurotransmission

[Retracted] MicroRNA‐346‐5p Regulates Differentiation of Bone Marrow‐Derived Mesenchymal Stem Cells by Inhibiting Transmembrane Protein 9

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