Rehabilitation Research Chair, College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Clin Interv Aging. 2021 Jan 8;16:57-70. doi: 10.2147/CIA.S285689. eCollection 2021.
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.
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.
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 , , and 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.
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, , , and genes.
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.
miRNA 在组织液中的释放，使其成为评估老年患者轻度认知障碍（MCI）进展和发病机制的非侵入性诊断生物标志物。
评估循环 miRNA 在 MCI 发病机制中的潜在作用及其与细胞氧化应激、细胞凋亡以及循环脑源性神经营养因子（BDNF）、Sirtuin 1（SIRT1）和二肽基肽酶 4（DPP4）的关系，研究对象为患有 MCI 的老年人。
本研究共纳入 150 名年龄为 65.4±3.7 岁的受试者。将参与者分为两组：健康正常组（n=80）和 MCI 组（n=70）。通过实时 PCR 分析来估计 miRNA 的相对表达水平；miR-124a、miR-483-5p、miR-142-3p 和 miR-125b 以及凋亡相关基因、和在 MCI 和对照组受试者的血清中的表达。此外，通过比色法估计氧化应激参数（MDA、NO、SOD 和 CAT）以及血浆 DPP4 活性、BDNF 和 SIRT1 水平。
与对照组相比，MCI 患者血清中 miR-124a 和 miR-483-5p 的水平显著升高，miR-142-3p 和 miR-125b 的水平显著降低。表达的 miRNA 与 MMSE、MoCA、ADL 和记忆评分测量的严重认知下降显著相关。与对照组相比，MCI 受试者中 Bax 和 caspase-3 凋亡诱导基因的表达显著增加，Bcl-2 抗凋亡基因的表达显著降低。此外，与对照组相比，MCI 受试者的血浆 MDA、NO 和 DPP4 活性水平显著升高，SOD、CAT、BDNF 和 SIRT1 水平显著降低。表达的 miRNA 与 NO、MDA、DPP4 活性、BDNF 和 SIRT-1 呈正相关，与 CAT、SOD、、和 基因呈负相关。
循环 miR-124a、miR-483-5p、miR-142-3p 和 miR-125b 与 MCI 患者严重认知下降、细胞氧化应激和细胞凋亡显著相关。因此，它可能是一种具有高诊断性能的 MCI 诊断的潜在非侵入性生物标志物。
