Objectives: Major depressive disorder (MDD) is a common illness worldwide and there is compelling evidence that epigenetic factors contribute to the manifestation of depression. Recently, exosomes have been found in many cell types and have become increasingly common target for molecular research in MDD. The exosomes enriched with miRNAs are relatively innovative and promising as new biological markers for MDD.
Methods: We conducted an exploratory cross-sectional analysis of miRNA expression in plasma exosomes from young adults aged from 18 to 35 years old, which included 100 MDD participants and 50 healthy subjects. We then investigated how the miRNA with abnormally altered expression levels affected the covariation of multimodal brain imaging data in all MDD and healthy controls. Finally, we generated adenoviruses (AAVs) and injected this into mouse prefrontal areas to alter miRNA expression levels to confirm our findings from human data.
Results: The downregulation of miR-151a-3p was observed in MDD cases compared with healthy controls by small RNA sequencing and real-time PCR. Our imaging–epigenetic association results indicate that lower miR-151a-3p levels in MDD are associated with both lower fractional amplitude of low frequency fluctuations and lower grey matter volume in prefrontal area. We injected viruses into the prefrontal regions of mice to increase miR-151a-3p expression and found that depressive mood was significantly improved in mice experiencing chronic unpredictable stress.
Conclusion: Our study supports miR-151a-3p expression changes in peripheral exosomes as a potential clinical MDD biomarker.
Keywords: finite element model; major depressive disorder; miR-151a-3p
Ethical statement: All our procedures were approved by the Ethical Committee of School of Basic Medical Sciences, Shandong University (reference number: ECSBMSSDU2022 – 1-61). All participants willingly take part in this study and provided written informed consent.
Funding statement: This study was funded by the Independently Cultivate Innovative Teams of Jinan, Shandong Province (202228079).