The important roles of microRNAs in depression: new research progress and future prospects

Miao, Chenggui; Chang, Jun

doi:10.1007/s00109-021-02052-8

Cited by 11 publications

(7 citation statements)

References 129 publications

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“…In this study, we identified differentially expressed miRNAs and assessed their functions with use of high-throughput sequencing and bioinformatic analysis in an animal model of depression. Notably, miR-26a-3p was found to be significantly down-regulated in hippocampal DG tissues of depressed rats, suggesting that this differentially expressed miRNA might play an important role in the development and pathogenesis of depression (29). Previous studies from bioinformatical analysis predicted that miR-26a-3p involves numerous pathways, in particular pathways targeting some specific genes associated with the regulation of synaptic plasticity and development within the nervous system (30)(31)(32).…”

Section: Discussionmentioning

confidence: 97%

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: Discussionmentioning

confidence: 97%

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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“…Finally, miRNAs are linked to numerous cellular processes, including neurodevelopment, and have been implicated as biomarkers for neuropsychiatric conditions like schizophrenia and major depression [ 47 , 48 ]. Consequently, we sought to probe for differences in miRNA expression between our HC- and BD-NPC lines in addition to two others, GM08330 and GM05440, as described previously by Bavamian and colleagues [ 26 ].…”

Section: Resultsmentioning

confidence: 99%

Bipolar disorder-iPSC derived neural progenitor cells exhibit dysregulation of store-operated Ca2+ entry and accelerated differentiation

Hewitt,

Alural,

Tilak

et al. 2023

Mol Psychiatry

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While most of the efforts to uncover mechanisms contributing to bipolar disorder (BD) focused on phenotypes at the mature neuron stage, little research has considered events that may occur during earlier timepoints of neurodevelopment. Further, although aberrant calcium (Ca2+) signaling has been implicated in the etiology of this condition, the possible contribution of store-operated Ca2+ entry (SOCE) is not well understood. Here, we report Ca2+ and developmental dysregulations related to SOCE in BD patient induced pluripotent stem cell (iPSC)-derived neural progenitor cells (BD-NPCs) and cortical-like glutamatergic neurons. First, using a Ca2+ re-addition assay we found that BD-NPCs and neurons had attenuated SOCE. Intrigued by this finding, we then performed RNA-sequencing and uncovered a unique transcriptome profile in BD-NPCs suggesting accelerated neurodifferentiation. Consistent with these results, we measured a slower rate of proliferation, increased neurite outgrowth, and decreased size in neurosphere formations with BD-NPCs. Also, we observed decreased subventricular areas in developing BD cerebral organoids. Finally, BD NPCs demonstrated high expression of the let-7 family while BD neurons had increased miR-34a, both being microRNAs previously implicated in neurodevelopmental deviations and BD etiology. In summary, we present evidence supporting an accelerated transition towards the neuronal stage in BD-NPCs that may be indicative of early pathophysiological features of the disorder.

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“…Increased enzyme activity of PTGS1 and PTGS2 has been implicated as another mechanism in depression, and herb drugs reducing arachidonic acid levels through inhibiting PTGS1/2 could be used to treat depression in the chronic unpredictable mild stress rat model [ 59 ]. Previous studies have shown that miRNAs participate in a series of important pathophysiological processes of depression, but none have been investigated in OSA-related depression [ 60 ]. For the first time, we found that miR-15b-5p/miR-92b-3p mimics could inhibit MAOA activity through directly targeting PTGS1 via NF-κB1/SP1 signaling and may be developed as new drug targets for depression treatment in OSA patients.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Sequencing Analysis in Obstructive Sleep Apnea and Depression: Anti-Oxidant and MAOA-Inhibiting Effects of miR-15b-5p and miR-92b-3p through Targeting PTGS1-NF-κB-SP1 Signaling

Chen

Hsu

et al. 2021

Antioxidants

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The aim of this study was to identify novel microRNAs related to obstructive sleep apnea (OSA) characterized by intermittent hypoxia with re-oxygenation (IHR) injury. Illumina MiSeq was used to identify OSA-associated microRNAs, which were validated in an independent cohort. The interaction between candidate microRNA and target genes was detected in the human THP-1, HUVEC, and SH-SY5Y cell lines. Next-generation sequencing analysis identified 22 differentially expressed miRs (12 up-regulated and 10 down-regulated) in OSA patients. Enriched predicted target pathways included senescence, adherens junction, and AGE-RAGE/TNF-α/HIF-1α signaling. In the validation cohort, miR-92b-3p and miR-15b-5p gene expressions were decreased in OSA patients, and negatively correlated with an apnea hypopnea index. PTGS1 (COX1) gene expression was increased in OSA patients, especially in those with depression. Transfection with miR-15b-5p/miR-92b-3p mimic in vitro reversed IHR-induced early apoptosis, reactive oxygen species production, MAOA hyperactivity, and up-regulations of their predicted target genes, including PTGS1, ADRB1, GABRB2, GARG1, LEP, TNFSF13B, VEGFA, and CXCL5. The luciferase assay revealed the suppressed PTGS1 expression by miR-92b-3p. Down-regulated miR-15b-5p/miR-92b-3p in OSA patients could contribute to IHR-induced oxidative stress and MAOA hyperactivity through the eicosanoid inflammatory pathway via directly targeting PTGS1-NF-κB-SP1 signaling. Over-expression of the miR-15b-5p/miR-92b-3p may be a new therapeutic strategy for OSA-related depression.

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The important roles of microRNAs in depression: new research progress and future prospects

Cited by 11 publications

References 129 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

Bipolar disorder-iPSC derived neural progenitor cells exhibit dysregulation of store-operated Ca2+ entry and accelerated differentiation

MicroRNA Sequencing Analysis in Obstructive Sleep Apnea and Depression: Anti-Oxidant and MAOA-Inhibiting Effects of miR-15b-5p and miR-92b-3p through Targeting PTGS1-NF-κB-SP1 Signaling

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