Cited by 228Extracellular vesicles in diseaseMicroRNA in disease regulationTreatment of Major Depression

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Exosomes from patients with major depression cause depressive-like behaviors in mice with involvement of miR-139-5p-regulated neurogenesis.

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Wei, Ze-Xu, Xie, Guo-Jun, Mao, Xiao, Zou, Xin-Peng, Liao, Ya-Jin, Liu, Qing-Shan, Wang, Hua, Cheng, Yong·2020·Neuropsychopharmacology

DOI 10.1038/s41386-020-0622-2PMC PMC7162931

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Abstract

Exosomal microRNAs (miRNAs) have been suggested to participate in the pathogenesis of neuropsychiatric diseases, but their role in major depressive disorder (MDD) is unknown. We performed a genome-wide miRNA expression profiling of blood-derived exosomes from MDD patients and control subjects and revealed the top differentially expressed exosomal miRNA, i.e. hsa-miR-139-5p (upregulation), had good performance to differentiate between MDD patients and controls. Tail vein injection of blood exosomes isolated from MDD patients into normal mice caused their depressive-like behaviors as determined by the forced swimming, tail suspension, and novelty suppressed feeding tests, and injection of blood exosomes isolated from healthy volunteers into unpredictable mild stress (CUMS)-treated mice alleviated their depressive-like behaviors. CUMS mice also showed significantly increased blood and brain levels of exosomal miR-139-5p. Furthermore, the depressive-like behaviors in CUMS-treated mice were rescued by intranasal injection of miR-139-5p antagomir, suggesting that increased exosomal miR-139-5p levels may mediate stress-induced depression-like behavior in mice. Both exosome treatment and miR-139-5p antagomir treatment increased hippocampal neurogenesis in the CUMS-treated mice, and treatment of exosome from MDD patients decreased hippocampal neurogenesis in the normal mice. The role of miR-139-5p in neurogenesis was validated by in vitro experiments, demonstrating that miR-139-5p is a negative regulator for neural stem cell proliferation and neuronal differentiation. Our findings together suggest that exosomes from patients with major depression caused depressive-like behaviors in mice with involvement of miR-139-5p-regulated neurogenesis. Therefore, exosomal miRNAs are promising targets for the diagnosis and treatment of MDD.

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Authors: Wei, Z.-X., Xie, G.-J., Mao, X., Zou, X.-P., Liao, Y.-J., Liu, Q.-S., Wang, H., & Cheng, Y.
Affiliations: Minzu University of China (CN)
Hunan Provincial Maternal and Child Health Hospital (CN)
Corresponding author: Cheng, Yong
ORCID: Mao, Xiao
Wang, Hua
Cheng, Yong
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2020-01-27
Volume: 45
Issue: 6
Pages: 1050-1058
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/s41386-020-0622-2
PMC: PMC7162931
OpenAlex: W3003054559
Cited by: 227
References: 40
Citations by year: 2026: 16 · 2025: 50 · 2024: 38 · 2023: 55 · 2022: 31 · 2021: 25 · 2020: 12
FWCI: 9.97
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Neuropsychopharmacology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Natural Science Foundation of China (81703492)
Natural Science Foundation of Beijing Municipality (7182092)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords: major depressive disorder, exosomes, exosomal microRNAs, miR-139-5p, neurogenesis, hippocampus, chronic unpredictable mild stress, depression-like behavior, neural stem cell proliferation, neuronal differentiation, antagomir, biomarkers
MeSH terms: Animals, Depression, Major Depressive Disorder, Humans, MicroRNAs, Mice, Exosomes, Neurogenesis

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Exosomes from patients with major depression cause depressive-like behaviors in mice with involvement of miR-139-5p-regulated neurogenesis.

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