Exploring the role of neuronal-enriched extracellular vesicle miR-93 and interoception in major depressive disorder.

Autor: Burrows K; Laureate Institute for Brain Research, Tulsa, OK, USA. kburrows@laureateinstitute.org., Figueroa-Hall LK; Laureate Institute for Brain Research, Tulsa, OK, USA.; Oxley College of Health and Natural Sciences, University of Tulsa, Tulsa, OK, USA., Stewart JL; Laureate Institute for Brain Research, Tulsa, OK, USA.; Oxley College of Health and Natural Sciences, University of Tulsa, Tulsa, OK, USA., Alarbi AM; Departments of Surgery and Psychiatry, School of Community Medicine, The University of Oklahoma, Tulsa, OK, USA., Kuplicki R; Laureate Institute for Brain Research, Tulsa, OK, USA., Hannafon BN; Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Tan C; Departments of Surgery and Psychiatry, School of Community Medicine, The University of Oklahoma, Tulsa, OK, USA., Risbrough VB; Center of Excellence for Stress and Mental Health, La Jolla, CA, USA.; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA., McKinney BA; Department of Mathematics and Computer Science, University of Tulsa, Tulsa, OK, USA., Ramesh R; Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Victor TA; Laureate Institute for Brain Research, Tulsa, OK, USA., Aupperle R; Laureate Institute for Brain Research, Tulsa, OK, USA.; Oxley College of Health and Natural Sciences, University of Tulsa, Tulsa, OK, USA., Savitz J; Laureate Institute for Brain Research, Tulsa, OK, USA.; Oxley College of Health and Natural Sciences, University of Tulsa, Tulsa, OK, USA., Teague TK; Departments of Surgery and Psychiatry, School of Community Medicine, The University of Oklahoma, Tulsa, OK, USA.; Department of Biochemistry and Microbiology, The Oklahoma State University Center for Health Sciences, Tulsa, OK, USA.; Department of Pharmaceutical Sciences, The University of Oklahoma College of Pharmacy, Oklahoma City, OK, USA., Khalsa SS; Laureate Institute for Brain Research, Tulsa, OK, USA.; Oxley College of Health and Natural Sciences, University of Tulsa, Tulsa, OK, USA., Paulus MP; Laureate Institute for Brain Research, Tulsa, OK, USA.; Oxley College of Health and Natural Sciences, University of Tulsa, Tulsa, OK, USA.
Jazyk: angličtina
Zdroj: Translational psychiatry [Transl Psychiatry] 2024 Apr 27; Vol. 14 (1), pp. 199. Date of Electronic Publication: 2024 Apr 27.
DOI: 10.1038/s41398-024-02907-x
Abstrakt: Major depressive disorder (MDD) is associated with interoceptive processing dysfunctions, but the molecular mechanisms underlying this dysfunction are poorly understood. This study combined brain neuronal-enriched extracellular vesicle (NEEV) technology and serum markers of inflammation and metabolism with Functional Magnetic Resonance Imaging (fMRI) to identify the contribution of gene regulatory pathways, in particular micro-RNA (miR) 93, to interoceptive dysfunction in MDD. Individuals with MDD (n = 41) and healthy comparisons (HC; n = 35) provided blood samples and completed an interoceptive attention task during fMRI. EVs were separated from plasma using a precipitation method. NEEVs were enriched by magnetic streptavidin bead immunocapture utilizing a neural adhesion marker (L1CAM/CD171) biotinylated antibody. The origin of NEEVs was validated with two other neuronal markers - neuronal cell adhesion molecule (NCAM) and ATPase Na+/K+ transporting subunit alpha 3 (ATP1A3). NEEV specificities were confirmed by flow cytometry, western blot, particle size analyzer, and transmission electron microscopy. NEEV small RNAs were purified and sequenced. Results showed that: (1) MDD exhibited lower NEEV miR-93 expression than HC; (2) within MDD but not HC, those individuals with the lowest NEEV miR-93 expression had the highest serum concentrations of interleukin (IL)-1 receptor antagonist, IL-6, tumor necrosis factor, and leptin; and (3) within HC but not MDD, those participants with the highest miR-93 expression showed the strongest bilateral dorsal mid-insula activation during interoceptive versus exteroceptive attention. Since miR-93 is regulated by stress and affects epigenetic modulation by chromatin re-organization, these results suggest that healthy individuals but not MDD participants show an adaptive epigenetic regulation of insular function during interoceptive processing. Future investigations will need to delineate how specific internal and external environmental conditions contribute to miR-93 expression in MDD and what molecular mechanisms alter brain responsivity to body-relevant signals.
(© 2024. The Author(s).)
Databáze: MEDLINE
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