Neuron-derived extracellular vesicles enriched from plasma show altered size and miRNA cargo as a function of antidepressant drug response.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
26
08
2020
accepted:
30
07
2021
revised:
27
07
2021
pubmed:
14
8
2021
medline:
15
3
2022
entrez:
13
8
2021
Statut:
ppublish
Résumé
Previous work has demonstrated that microRNAs (miRNAs) change as a function of antidepressant treatment (ADT) response. However, it is unclear how representative these peripherally detected miRNA changes are to those occurring in the brain. This study aimed to use peripherally extracted neuron-derived extracellular vesicles (NDEV) to circumvent these limitations and investigate neuronal miRNA changes associated with antidepressant response. Samples were collected at two time points (baseline and after 8 weeks of follow-up) from depressed patients who responded (N = 20) and did not respond (N = 20) to escitalopram treatment, as well as controls (N = 20). Total extracellular vesicles (EVs) were extracted from plasma, and then further enriched for NDEV by immunoprecipitation with L1CAM. EVs and NDEVs were characterized, and NDEV miRNA cargo was extracted and sequenced. Subsequently, studies in cell lines and postmortem tissue were conducted. Characterization of NDEVs revealed that they were smaller than other EVs isolated from plasma (p < 0.0001), had brain-specific neuronal markers, and contained miRNAs enriched for brain functions (p < 0.0001) Furthermore, NDEVs from depressed patients were smaller than controls (p < 0.05), and NDEV size increased with ADT response (p < 0.01). Finally, changes in NDEV cargo, specifically changes in miR-21-5p, miR-30d-5p, and miR-486-5p together (p < 0.01), were associated with ADT response. Targets of these three miRNAs were altered in brain tissue from depressed individuals (p < 0.05). Together, this study indicates that changes in peripherally isolated NDEV can act as both a clinically accessible and informative biomarker of ADT response specifically through size and cargo.
Identifiants
pubmed: 34385599
doi: 10.1038/s41380-021-01255-2
pii: 10.1038/s41380-021-01255-2
doi:
Substances chimiques
Antidepressive Agents
0
MicroRNAs
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7417-7424Subventions
Organisme : CIHR
ID : FDN148374
Pays : Canada
Organisme : CIHR
ID : EGM141899
Pays : Canada
Organisme : CIHR
ID : EPN161427
Pays : Canada
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
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