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Cited by 90Treatment of Major DepressionMicroRNA in disease regulationStress Responses and Cortisol

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

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Li, Ye, Fan, Cuiqin, Wang, Liyan, Lan, Tian, Gao, Rui, Wang, Wenjing, Yu, Shu Yan·2021·Journal of Clinical Investigation
DOI 10.1172/jci148853PMC PMC8363293
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Abstract

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 the hippocampus and found that miR-26a-3p was markedly downregulated in a rat model of depression, whereas upregulation of miR-26a-3p within DG regions rescued the neuronal deterioration and depression-like phenotypes resulting from stress exposure, effects that appear to be mediated by the PTEN pathway. The knockdown of miR-26a-3p in DG regions of normal control rats induced depression-like behaviors, effects that were accompanied by activation of the PTEN/PI3K/Akt signaling pathway and neuronal deterioration via suppression of autophagy, impairments in synaptic plasticity, and promotion of neuronal apoptosis. In conclusion, these results suggest that 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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  • miR-26a-3p and miR-132 can induce depressive symptoms by activating the PTEN/PI3K/Akt signaling pathway.

    “miR-26a-3p263 and miR-132264 can induce depressive symptoms by activating the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/Akt signaling pathway”

    From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [263]

    This citation is attached to miR-26a-3p, not miR-132. The paper reports the opposite direction of effect: upregulating miR-26a-3p rescued depression-like behavior (p. 1), while knocking it down increased PTEN, reduced PI3K and phosphorylated Akt (Results, p. 5), and induced depression-like behavior. (LLM, conf=0.90)

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Cited by

Sorted by citations

Authors
Li, Y., Fan, C., Wang, L., Lan, T., Gao, R., Wang, W., & Yu, S. Y.
Affiliations
  • Shandong University (CN)
  • Jinan Vocational College of Nursing (CN)
Corresponding author
Yu, Shu Yan
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2021-08-16
Volume
131
Issue
16
ISSN
  • 0021-9738 (ISSN-L)
  • 1558-8238
DOI
10.1172/jci148853
PMC
PMC8363293
OpenAlex
W3178401932
Cited by
90
References
6
Citations by year
2026: 13 · 2025: 19 · 2024: 24 · 2023: 22 · 2022: 10 · 2021: 2
FWCI
8.46
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
the National Natural Science Foundation of China ; Natural Science Foundation of Shandong Province of China; Fundamental Research Funds of Shandong University (NSFC81873796,82071513,ZR2020ZD25,2018JC008)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
depression, hippocampus, dentate gyrus, PTEN/PI3K/AKT signaling, autophagy, synaptic plasticity, neuronal apoptosis, chronic stress, miRNA expression profiling, therapeutic target
MeSH terms
Animals, Autophagy, Depression, Disease Models, Animal, Hippocampus, Male, Synaptic Transmission, Neuronal Plasticity, Neurons, Signal Transduction, Rats, Wistar, Apoptosis, Dentate Gyrus, Phosphatidylinositol 3-Kinases, MicroRNAs, Proto-Oncogene Proteins c-akt, PTEN Phosphohydrolase, Rats, Gene Knockdown Techniques, Transcriptome

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