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Circulating microRNAs and Molecular Oxidative Stress in Older Adults with Neuroprogression Disorders
Hadeel A Al-Rawaf1, Ahmad H Alghadir2, Sami A Gabr2
1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.
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.
Insights
Circulating microRNAs (miRNAs) show altered expression in older adults with depression, correlating with stress hormones and oxidative stress. These miRNAs may serve as diagnostic biomarkers and therapeutic targets for depression.
Area of Science:
- Biochemistry
- Genetics
- Neuroscience
Background:
- Circulating microRNAs (miRNAs) are potential biomarkers for diseases, including depression.
- These molecules regulate gene expression in normal and diseased cells.
- Their role in depression among older adults, linked to stress hormones and oxidative stress, requires investigation.
Purpose of the Study:
- To evaluate the role of circulating miRNAs in older adults with depression.
- To assess the association of these miRNAs with stress hormones (cortisol, serotonin) and cellular oxidative stress.
Main Methods:
- 70 participants were classified into healthy (n=30) and depression (n=40) groups.
- Expression of miR-124, miR-34a-5p, miR-135, and miR-451-a was measured using RT-PCR.
- Correlation with oxidative stress markers (NO, SOD2, CAT, iNOS) and hormones (cortisol, serotonin) was analyzed.
Main Results:
- Depression was present in 57.14% of participants.
- Depressed individuals showed altered miRNA expression (miR-124, miR-34a-5p increased; miR-135, miR-451-a decreased) compared to controls.
- Increased cortisol, decreased serotonin, elevated NO, and altered antioxidant gene expression were observed in depressed subjects.
Conclusions:
- Circulating miRNAs, oxidative stress, and hormonal levels are implicated in depression among older adults.
- These miRNAs may play a regulatory role in depression progression.
- miRNAs show potential as prognostic biomarkers and therapeutic targets for depression.
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