Abstract
The intracellular microRNAs that negatively regulate Toll-like receptor 4 signaling pathways in peripheral blood mononuclear cells are associated with major depressive disorder (MDD). However, that the distribution of these microRNAs in exosomes could be a biomarker of central nervous system diseases is just beginning to be explored. In the present study, we isolated serum exosomes from patients with MDD and healthy controls to explore the levels of exosomal microRNAs, including let-7e, miR-21-5p, miR-223, miR-145, miR-146a, and miR-155. We also investigated the changes of these exosomal microRNAs after antidepressant treatment and their association with clinical changes in scores on the Hamilton Depression Rating Scale. An ANCOVA adjusted by age, sex, BMI, and smoking showed higher expression levels of miR-146a (p = 0.006) in patients with MDD compared to controls. Patients who achieved remission showed significantly lower let-7e, miR-21-5p, miR-145, miR-146a, and miR-155 levels before treatment and increased levels after antidepressant treatment compared with the non-remission group. Through receiver operating characteristic (ROC) analysis, let-7e, miR-145, and miR-146a showed acceptable discrimination between the remission and non-remission groups, whereas miR-21-5p and miR-155 showed poor discrimination. These findings demonstrate that exosomal microRNAs may play essential roles in predicting antidepressants response.
Highlights
Depression is among the most common and costly of all psychiatric disorders
We investigated the microRNA expression profiles of negatively regulating TLR4 signaling, including the measurement of let-7e, miR-21-5p, miR-223, miR-145, miR-146a, and miR-155 in the serum exosome obtained from patients with major depressive disorder (MDD) before and after treatment with antidepressants
Age and body mass index (BMI) were similar in healthy controls and MDD patients before treatment
Summary
Depression is among the most common and costly of all psychiatric disorders. Nearly one in four women and one in six men experience at least one clinically defined depression episode in their lifetimes. Major depression is etiologically related to the peripheral and central innate immune systems, especially aberrant Toll-like receptor (TLR) expression [2,3,4]. The negative regulators of TLR signal pathways that prevent TLR-induced cytokine storms by controlling the magnitude and duration of responses play essential roles in the development of major depressive disorder (MDD) [5,6]. Exosomes are thought to be able to change the behavior of recipient cells and act as key players in many cellular and molecular pathways in mental disorders [7,8]. Plasma exosomes can deliver sigma-1 receptors to the central nervous system, ameliorate inflammation, and improve depressive-like behavior in animals [9]. The differential expression of microRNAs in the exosomes of the rat model was associated with the MAPK pathway, Wnt pathway, and mTOR pathway [10]
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