Amanzadeh Jajin Elnaz, Esmaeili Abolghasem, Rahgozar Soheila, Noorbakhshnia Maryam
Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.
Department of Plant and Animal Biology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.
Front Neurosci. 2021 Feb 25;14:598617. doi: 10.3389/fnins.2020.598617. eCollection 2020.
Alzheimer's disease (AD) is a neurodegenerative disease with cognitive impairment. Oxidative stress in neurons is considered as a reason for development of AD. Antioxidant agents such as quercetin slow down AD progression, but the usage of this flavonoid has limitations because of its low bioavailability. We hypothesized that quercetin-conjugated superparamagnetic iron oxide nanoparticles (QT-SPIONs) have a better neuroprotective effect on AD than free quercetin and regulates the antioxidant, apoptotic, and APP gene, and miRNA-101. In this study, male Wistar rats were subjected to AlCl, AlCl + QT, AlCl + SPION, and AlCl + QT-SPION for 42 consecutive days. Behavioral tests and qPCR were used to evaluate the efficiency of treatments. Results of behavioral tests revealed that the intensity of cognitive impairment was decelerated at both the middle and end of the treatment period. The effect of QT-SPIONs on learning and memory deficits were closely similar to the control group. The increase in expression levels of APP gene and the decrease in mir101 led to the development of AD symptoms in rats treated with AlCl while these results were reversed in the AlCl + QT-SPIONs group. This group showed similar results with the control group. QT-SPION also decreased the expression levels of antioxidant enzymes along with increases in expression levels of anti-apoptotic genes. Accordingly, the antioxidant effect of QT-SPION inhibited progression of cognitive impairment sustaining the balance of antioxidant enzymes in the hippocampus of AD model rats.
阿尔茨海默病(AD)是一种伴有认知障碍的神经退行性疾病。神经元中的氧化应激被认为是AD发病的一个原因。槲皮素等抗氧化剂可减缓AD的进展,但由于这种类黄酮的生物利用度低,其应用存在局限性。我们推测,槲皮素偶联的超顺磁性氧化铁纳米颗粒(QT-SPIONs)对AD的神经保护作用比游离槲皮素更好,并能调节抗氧化、凋亡和APP基因以及miRNA-101。在本研究中,雄性Wistar大鼠连续42天接受AlCl、AlCl + QT、AlCl + SPION和AlCl + QT-SPION处理。采用行为测试和qPCR评估治疗效果。行为测试结果显示,在治疗期的中期和末期,认知障碍的强度均有所减缓。QT-SPIONs对学习和记忆缺陷的影响与对照组非常相似。APP基因表达水平的升高和mir101的降低导致AlCl处理的大鼠出现AD症状,而在AlCl + QT-SPIONs组中这些结果得到了逆转。该组与对照组结果相似。QT-SPION还降低了抗氧化酶的表达水平,同时增加了抗凋亡基因的表达水平。因此,QT-SPION的抗氧化作用抑制了认知障碍的进展,维持了AD模型大鼠海马中抗氧化酶的平衡。