Molecular Changes in Circulating microRNAs' Expression and Oxidative Stress in Adults with Mild Cognitive Impairment: A Biochemical and Molecular Study.
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.
['Al-Rawaf|Hadeel A|HA|', 'Alghadir|Ahmad H|AH|', 'Gabr|Sami A|SA|0000-0003-4965-5852']
D000368:Aged D000369:Aged, 80 and over D015415:Biomarkers D016022:Case-Control Studies D000074166:Circulating MicroRNA D060825:Cognitive Dysfunction D018819:Dipeptidyl Peptidase 4 D005260:Female D006801:Humans D008297:Male D035683:MicroRNAs D008875:Middle Aged D018384:Oxidative Stress D060888:Real-Time Polymerase Chain Reaction D015854:Up-Regulation
biomarkers MCI circulating miRNAs cellular oxidative stress apoptosis real-time RT-PCR