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Molecular Changes in Circulating microRNAs' Expression and Oxidative Stress in Adults with Mild Cognitive Impairment:
Hadeel A Al-Rawaf1,2, Ahmad H Alghadir1, Sami A Gabr1
1Rehabilitation Research Chair, College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Background:
The release of miRNAs in tissue fluids significantly recommends its use as non-invasive diagnostic biomarkers for the progression and pathogenesis of mild cognitive impairment (MCI) in aged patients.
Objective:
The potential role of circulated miRNAs in the pathogenesis of MCI and its association with cellular oxidative stress, apoptosis, and circulated BDNF, Sirtuin 1 (SIRT1), and dipeptidyl peptidase-4 (DPP4) were evaluated in older adults with MCI.
Methods:
A total of 150 subjects aged 65.4±3.7 years were recruited in this study. The participants were classified into two groups: healthy normal (n=80) and MCI (n=70). Real-time PCR analysis was performed to estimate the relative expression of miRNAs; miR-124a, miR-483-5p, miR-142-3p, and miR-125b, and apoptotic-related genes Bax, Bcl-2, and caspase-3 in the sera of MCI and control subjects. In addition, oxidative stress parameters; MDA, NO, SOD, and CAT; as well as plasma DPP4 activity, BDNF, SIRT1 levels were colorimetrically estimated.
Results:
The levels of miR-124a and miR-483-5p significantly increased and miR-142-3p and miR-125b significantly reduced in the serum of MCI patients compared to controls. The expressed miRNAs significantly correlated with severe cognitive decline, measured by MMSE, MoCA, ADL, and memory scores. The expression of Bax, and caspase-3 apoptotic inducing genes significantly increased and Bcl-2 antiapoptotic gene significantly reduced in MCI subjects compared to controls. In addition, the plasma levels of MDA, NO, and DPP4 activity significantly increased, and the levels of SOD, CAT, BDNF, and SIRT1 significantly reduced in MCI subjects compared to controls. The expressed miRNAs correlated positively with NO, MDA, DPP4 activity, BDNF, and SIRT-1, and negatively with the levels of CAT, SOD, Bcl-2, Bax, and caspase-3 genes.
Conclusion:
Circulating miR-124a, miR-483-5p, miR-142-3p, and miR-125b significantly associated with severe cognitive decline, cellular oxidative stress, and apoptosis in patients with MCI. Thus, it could be potential non-invasive biomarkers for the diagnosis of MCI with high diagnostic performance.
Insights
Circulating microRNAs (miRNAs) show significant association with cognitive decline, oxidative stress, and apoptosis in mild cognitive impairment (MCI) patients. These miRNAs hold potential as non-invasive biomarkers for diagnosing MCI.
Area of Science:
- Biochemistry
- Molecular Biology
- Neuroscience
Background:
- MicroRNAs (miRNAs) released in bodily fluids are promising non-invasive biomarkers for mild cognitive impairment (MCI) progression.
- Investigating circulating miRNAs aids in understanding MCI pathogenesis, particularly its links to oxidative stress and apoptosis.
Purpose of the Study:
- To evaluate the role of circulating miRNAs in MCI pathogenesis.
- To assess the association of miRNAs with cellular oxidative stress, apoptosis, BDNF, Sirtuin 1 (SIRT1), and dipeptidyl peptidase-4 (DPP4) in older adults with MCI.
Main Methods:
- Real-time PCR was used to measure serum levels of miR-124a, miR-483-5p, miR-142-3p, miR-125b, and apoptotic genes (Bax, Bcl-2, caspase-3) in 150 subjects (80 controls, 70 MCI).
- Oxidative stress markers (MDA, NO, SOD, CAT), plasma DPP4 activity, BDNF, and SIRT1 levels were colorimetrically assessed.
Main Results:
- Specific miRNAs (miR-124a, miR-483-5p) increased while others (miR-142-3p, miR-125b) decreased in MCI patients.
- MCI patients exhibited increased apoptotic markers (Bax, caspase-3), decreased anti-apoptotic marker (Bcl-2), elevated oxidative stress (MDA, NO), and reduced antioxidants (SOD, CAT).
- Circulating miRNAs correlated significantly with cognitive decline, oxidative stress, apoptosis markers, and levels of BDNF, SIRT1, and DPP4.
Conclusions:
- Circulating miRNAs are significantly associated with cognitive decline, oxidative stress, and apoptosis in MCI.
- These miRNAs demonstrate potential as non-invasive diagnostic biomarkers for MCI with high diagnostic performance.
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