Exosomes from patients with major depression cause depressive-like behaviors in mice with involvement of miR-139-5p-regulated neurogenesis.
Open accessAbstract
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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In MMD, miRNAs are involved in the pathogenesis of the disease.
“In MMD, it has been reported that miRNAs are not only involved in the pathogenesis of the disease [17], but are also associated with depression caused by various illnesses [18, 19], as well as the response to specific treatments such as isoliquiritin [20], oligonucleotides [21], or purinergic receptor [22], confirming their potential as disease monitoring biomarkers.”
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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
- Venue
- Neuropsychopharmacology
- Published
- 2020-01-27
- Volume
- 45
- Issue
- 6
- Pages
- 1050-1058
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- 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
- 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 › 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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