Profiling Small RNA From Brain Extracellular Vesicles in Individuals With Depression.

Autor:	Ibrahim P; Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada.; McGill Group for Suicide Studies, Douglas Mental Health University Institute, Verdun, Quebec, Canada., Denniston R; McGill Group for Suicide Studies, Douglas Mental Health University Institute, Verdun, Quebec, Canada., Mitsuhashi H; Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada.; McGill Group for Suicide Studies, Douglas Mental Health University Institute, Verdun, Quebec, Canada., Yang J; McGill Group for Suicide Studies, Douglas Mental Health University Institute, Verdun, Quebec, Canada., Fiori LM; McGill Group for Suicide Studies, Douglas Mental Health University Institute, Verdun, Quebec, Canada., Żurawek D; McGill Group for Suicide Studies, Douglas Mental Health University Institute, Verdun, Quebec, Canada., Mechawar N; Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada.; McGill Group for Suicide Studies, Douglas Mental Health University Institute, Verdun, Quebec, Canada.; Department of Psychiatry, McGill University, Montreal, Quebec, Canada., Nagy C; Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada.; McGill Group for Suicide Studies, Douglas Mental Health University Institute, Verdun, Quebec, Canada.; Department of Psychiatry, McGill University, Montreal, Quebec, Canada., Turecki G; Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada.; McGill Group for Suicide Studies, Douglas Mental Health University Institute, Verdun, Quebec, Canada.; Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
Jazyk:	angličtina
Zdroj:	The international journal of neuropsychopharmacology [Int J Neuropsychopharmacol] 2024 Mar 01; Vol. 27 (3).
DOI:	10.1093/ijnp/pyae013
Abstrakt:	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. (© The Author(s) 2024. Published by Oxford University Press on behalf of CINP.)
Databáze:	MEDLINE
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