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老年猫脑中金属硫蛋白I/II表达及金属离子水平与β淀粉样蛋白沉积的相关性

Metallothionein I/II Expression and Metal Ion Levels in Correlation with Amyloid Beta Deposits in the Aged Feline Brain.

作者信息

Apostolopoulou Emmanouela P, Raikos Nikolaos, Vlemmas Ioannis, Michaelidis Efstratios, Brellou Georgia D

机构信息

Department of Pathology, Faculty of Health Sciences, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54627 Thessaloniki, Greece.

Department of Forensic Medicine & Toxicology, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.

出版信息

Brain Sci. 2023 Jul 22;13(7):1115. doi: 10.3390/brainsci13071115.

Abstract

Brain aging has been correlated with high metallothionein I-II (MT-I/II) expression, iron and zinc dyshomeostasis, and Aβ deposition in humans and experimental animals. In the present study, iron and zinc accumulation, the expression of MT-I/II and Aβ42, and their potential association with aging in the feline brain were assessed. Tissue sections from the temporal and frontal grey (GM) and white (WM) matter, hippocampus, thalamus, striatum, cerebellum, and dentate nucleus were examined histochemically for the presence of age-related histopathological lesions and iron deposits and distribution. We found, using a modified Perl's/DAB method, two types of iron plaques that showed age-dependent accumulation in the temporal GM and WM and the thalamus, along with the age-dependent increment in cerebellar-myelin-associated iron. We also demonstrated an age-dependent increase in MT-I/II immunoreactivity in the feline brain. In cats over 7 years old, Aβ immunoreactivity was detected in vessel walls and neuronal somata; extracellular Aβ deposits were also evident. Interestingly, Aβ-positive astrocytes were also observed in certain cases. ICP-MS analysis of brain content regarding iron and zinc concentrations showed no statistically significant association with age, but a mild increase in iron with age was noticed, while zinc levels were found to be higher in the Mature and Senior groups. Our findings reinforce the suggestion that cats could serve as a dependable natural animal model for brain aging and neurodegeneration; thus, they should be further investigated on the basis of metal ion concentration changes and their effects on aging.

摘要

脑老化与人类和实验动物体内金属硫蛋白I-II(MT-I/II)高表达、铁和锌稳态失衡以及β-淀粉样蛋白(Aβ)沉积相关。在本研究中,评估了猫脑中铁和锌的蓄积、MT-I/II和Aβ42的表达及其与衰老的潜在关联。对颞叶和额叶灰质(GM)、白质(WM)、海马体、丘脑、纹状体、小脑和齿状核的组织切片进行组织化学检查,以确定是否存在与年龄相关的组织病理学病变、铁沉积及其分布情况。我们使用改良的Perl氏/DAB方法发现,在颞叶GM、WM和丘脑中存在两种类型的铁斑,其呈现出与年龄相关的蓄积,同时小脑髓鞘相关铁也呈现出与年龄相关的增加。我们还证明了猫脑中MT-I/II免疫反应性随年龄增长而增加。在7岁以上的猫中,在血管壁和神经元胞体中检测到Aβ免疫反应性;细胞外Aβ沉积物也很明显。有趣的是,在某些情况下还观察到Aβ阳性星形胶质细胞。对脑内铁和锌浓度的电感耦合等离子体质谱(ICP-MS)分析显示,与年龄没有统计学上的显著关联,但注意到铁随年龄有轻度增加,而成熟组和老年组的锌水平较高。我们的研究结果进一步表明,猫可以作为脑老化和神经退行性变可靠的天然动物模型;因此,应基于金属离子浓度变化及其对衰老的影响对其进行进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8519/10377600/4e61fedb4968/brainsci-13-01115-g001.jpg

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