Abstract

Background circulating microRNAs are potential blood biomarkers differentially expressed in many diseases including neuro depression disorders. It controls the expression of human genes and associated cellular and physiological processes in normal and diseased cells. We aimed to evaluate the potential role of circulating miRNAs and their association with both stress hormones and cellular oxidative stress in neuro depression disorders occurred among older adults. Methods a total of 70 healthy subjects were included in this study. Based upon the profile of mood states (POMS-32 score), the participants classified into two groups; healthy subjects (n =30) and depression (n =40). The expression of microRNAs; miR-124, miR-34a-5p, miR-135, and miR-451-a and their correlation with cellular oxidative stress parameters; cellular NO, genes of SOD2, CAT and iNOS, and hormones; cortisol and serotonin were estimated by a quantitative real-time RT-PCR, high-performance liquid chromatography, and ELISA Immunoassay techniques, respectively. Results depression was reported in 57.14% of the participants. The results showed a significant increase (p =0.01) in the total mood scores, and relative depression domains in older adults with depression compared to healthy controls. The relative expression levels of miR-124, miR-34a-5p significantly increased and the expression levels of miR-135, and miR-451-a significantly decreased in older adults with depression compared to healthy controls. In addition, the levels of cortisol significantly increased and serotonin (5HT) significantly reduced in all participants with depression. Cellular oxidative stress analysis for depressed subjects showed that serum NO levels and the expression of iNO gene significantly increased conversely with a decline in the molecular expression antioxidative genes; SOD2, CAT, respectively. The results showed that cellular oxidative stress parameters correlated positively with depression scores, cortisol, and negatively with cellular serotonin levels. In depressed subjects, the relative expression of microRNAs correlated positively with depression score, NO, iNOS, cortisol, and negatively associated with SOD2, CAT, and serotonin. Conclusion The combination of cellular oxidative stress and hormonal levels strongly supports a role for circulating miRNAs; miR-124, miR-34a-5p, miR-135, and miR-451-a in the regulation of depression and mood disorders among older adults. The expressed microRNAs with their related association to cellular oxidative stress and adrenal hormones are a step towards understanding the role of these small RNA molecules in the progression of depression among older adults. Thus, cellular miRNAs might have a prognostic role in the diagnosis and as a target for treatment strategies in depressed subjects.

Highlights

  • MicroRNAs are non-coding RNAs differentially expressed in many diseases including neuro depression disorders [1,2,3,4,5,6,7,8]

  • Depression scores were evaluated by the profile of mood states (POMS-32) as previously reported [34, 35], and the subjects were classified according to Profile of Mood States (POMS)-32 into two groups: the control group (n =30), and the depressive group (n =40) as shown in the flow chart Figure 1

  • The results showed a significant increase (p =0.01) in the total mood scores, and relative depression domains in older adults with depression compared to healthy controls (Figure 2(a))

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Summary

Introduction

MicroRNAs (miRNAs) are non-coding RNAs differentially expressed in many diseases including neuro depression disorders [1,2,3,4,5,6,7,8]. Higher expression of cellular microRNAs was reported in neurons and proposed to regulate celluar processes of brain development including cellular neurogenesis, Disease Markers apoptosis, proliferation, and cellular metabolism [4, 10]. Abnormal or dysregulated expression of cellular miRNAs was significantly associated with many neurological and psychiatric diseases [5, 6, 11, 12]. The differntial expression of miRNAs is stable and its association with the status of cells could be detected [13]. In many diseases, microRNAs were the potential blood biomarkers displaying efficiently the magnitude of the disease on physiological and cellular bases [14]

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