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Profiling Small RNA From Brain Extracellular Vesicles in Individuals With Depression
Abstract
Background: Major depressive disorder (MDD) is a leading cause of disability with significant mortality risk. Despite progress in our understanding of the etiology of MDD, the underlying molecular changes in the brain remain poorly understood. Extracellular vesicles (EVs) are lipid-bound particles that can reflect the molecular signatures of the tissue of origin. We aimed to optimize a streamlined EV isolation protocol from postmortem brain tissue and determine whether EV RNA cargo, particularly microRNAs (miRNAs), have an MDD-specific profile. Methods: EVs were isolated from postmortem human brain tissue. Quality was assessed using western blots, transmission electron microscopy, and microfluidic resistive pulse sensing. EV RNA was extracted and sequenced on Illumina platforms. Functional follow-up was performed in silico. Results: Quality assessment showed an enrichment of EV markers, as well as a size distribution of 30 to 200 nm in diameter, and no contamination with cellular debris. Small RNA profiling indicated the presence of several RNA biotypes, with miRNAs and transfer RNAs being the most prominent. Exploring miRNA levels between groups revealed decreased expression of miR-92a-3p and miR-129-5p, which was validated by qPCR and was specific to EVs and not seen in bulk tissue. Finally, in silico functional analyses indicate potential roles for these 2 miRNAs in neurotransmission and synaptic plasticity. Conclusion: We provide a streamlined isolation protocol that yields EVs of high quality that are suitable for molecular follow-up. Our findings warrant future investigations into brain EV miRNA dysregulation in MDD.
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“However, it should be mentioned that recent study reported that miR-129-5p is decreased in exosomes isolated from the postmortem brain of males but not females that suffered from depression [77].”
From A role for astrocytic miR-129-5p in frontotemporal dementia (2025) · cites this paper as [77]
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Sex-specific transcriptional signatures in human depression
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Self-citationWei, Z.-X., Xie, G.-J., Mao, X., Zou, X.-P., Liao, Y.-J., Liu, Q.-S., Wang, H., & Cheng, Y. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-0622-2 · Cited by 227
miR-323a regulates ERBB4 and is involved in depression
Fiori, L. M., Kos, A., Lin, R., Théroux, J.-F., Lopez, J. P., Kühne, C., Eggert, C., Holzapfel, M., Huettl, R.-E., Mechawar, N., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00953-7 · Cited by 88 · cited 16×
“To determine whether these effects are specific to EVs, we correlated the expression of miRNAs from EVs to miRNA expression levels observed in bulk ACC tissue in the subjects that overlap with those from a previous study of our group (Fiori et al., 2021).”
BackgroundMethodResultInfluentialSelf-citationRapamycin reveals an mTOR-independent repression of Kv1.1 expression during epileptogenesis
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A role for astrocytic miR-129-5p in frontotemporal dementia
Kaurani, L., Pradhan, R., Schröder, S., Burkhardt, S., Schuetz, A.-L., Krüger, D. M., Pena, T., Heutink, P., Sananbenesi, F., & Fischer, A. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03338-y · Cited by 10
Metadata
- Authors
- Ibrahim, P., Denniston, R., Mitsuhashi, H., Yang, J., Fiori, L. M., Żurawek, D., Mechawar, N., Nagy, C., & Turecki, G.
- Affiliations
- Integrated Program in Neuroscience, McGill University , Montreal, Quebec , Canada
- McGill Group for Suicide Studies, Douglas Mental Health University Institute , Verdun, Quebec , Canada
- Venue
- International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2024-03-01
- Volume
- 27
- Issue
- 3
- ISSN
- 1461-1457
- 1469-5111
- PMC
- PMC10946232
- Cited by
- 29
- References
- 5
- Language
- en
- Funders
- Canadian Institute of Health Research (FDN148374, ENP161427)
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