Identification of Differential MicroRNAs in Cerebrospinal Fluid and Serum of Patients with Major Depressive Disorder

Abstract

Major depression is a debilitating disease. To date, the development of biomarkers of major depressive disorder (MDD) remains a challenge. Recently, alterations in the expression of microRNAs (miRNAs) from post-mortem brain tissue and peripheral blood have been linked to MDD. The goals of this study were to detect the differential miRNAs in cerebrospinal fluid (CSF) and serum of MDD patients. First, the relative expression levels of 179 miRNAs (relative high levels in serum) were analyzed by miRNA PCR Panel in the CSF of MDD patients. Then, the differentially altered miRNAs from CSF were further assessed by qRT-PCR in the serum of the same patients. Finally, the serum differentially altered miRNAs were further validated by qRT-PCR in the serum of another MDD patients. The CSF-results indicated that 11 miRNAs in MDD patients were significantly higher than these in control subjects, and 5 miRNAs were significantly lower than these in control subjects. The serum-results from the same patients showed that 3 miRNAs (miR-221-3p, miR-34a-5p, and let-7d-3p) of the 11 miRNAs were significantly higher than these in control subjects, and 1 miRNA (miR-451a) of 5 miRNAs was significantly lower than these in control subjects. The up-regulation of miR-221-3p, miR-34a-5p, let-7d-3p and down-regulation of miR-451a was further validated in another 32 MDD patients. ROC analysis showed that the area under curve of let-7d-3p, miR-34a-5p, miR-221-3p and miR-451a was 0.94, 0.98, 0.97 and 0.94, with specificity of 90.48%, 95.24%, 90.48% and 90.48%, and sensitivity of 93.75%, 96.88%, 90.63% and 84.85%, respectively. In addition, target gene prediction found that the altered miRNAs are involved in affecting some important genes and pathway related to MDD. Our results suggested that differentially altered miRNAs in CSF might be involved in MDD, and serum miR-221-3p, miR-34a-5p, let-7d-3p, and miR-451a might be able to serve as biomarkers for MDD.

MicroRNA-511 Binds to FKBP5 mRNA, Which Encodes a Chaperone Protein, and Regulates Neuronal Differentiation

“…Using miRNAs as potential biomarkers is also an appealing strategy because more and more effort is being directed at a personalized medicine approach. Our findings that miR-511 expression can be controlled by GR signaling suggest that it is possible that individuals with single nucleotide polymorphisms in FKBP5 may display altered miR-511 expression, which could be detected in serum or cerebrospinal fluid, as has been accomplished in patients with AD or major depression (29,34). This approach would permit selective targeting of miR-511 when warranted and could potentially enhance regulation of processes implicated in disease such as neurogenesis.…”

MicroRNAs in Psychological Stress Reactions and Their Use as Stress-Associated Biomarkers, Especially in Human Saliva

“…Alterations in several circulating miRNA expression levels have been found in psychiatric disorders such as major depressive disorder [64], schizophrenia [65], autism spectrum disorder [66], bipolar disorder [67], Alzheimer disease [68], and mild cognitive impairment [69]. All of these studies describe a possible use of miRNAs as biomarker for the respective disease, mainly in peripheral blood.…”

MicroRNA let-7d is a target of cannabinoid CB 1 receptor and controls cannabinoid signaling

“…¼ arbitrary units). Brites and Fernandes, 2015;Qu et al, 2015Wan et al, 2015 but are rather associated to the physiopathology of other tissues such as kidney and vascular endothelium (Aguado-Fraile et al, 2015;Lorenzen, 2015;Rudnicki et al, 2015). Thus, neither methanandamide nor morphine exposure changed the expression levels of hsa-miR-93 (F(8,97) ¼ 0.1882, P ¼ 0.9920) or hsa-miR-126 (F(8,95) ¼ 0.1639, P ¼ 0.9950) in SH-SY5Y cells (Fig.…”