Influence of Transgenic Metallothionein-1 on Gliosis, CA1 Neuronal Loss, and Brain Metal Levels of the Tg2576 Mouse Model of Alzheimer's Disease.
Influence of Transgenic Metallothionein-1 on Gliosis, CA1 Neuronal Loss, and Brain Metal Levels of the Tg2576 Mouse Model of Alzheimer's Disease.
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DOI：
10.3390/ijms18020251
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发表时间：
2017-01-26
影响因子：
5.6
通讯作者：
Hidalgo J
中科院分区：
文献类型：
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作者：
Comes G;Manso Y;Escrig A;Fernandez-Gayol O;Sanchis P;Molinero A;Giralt M;Carrasco J;Hidalgo J
阿尔茨海默病（AD）的小鼠模型Tg 2576小鼠（APP）提供了有价值的信息，例如金属硫蛋白（MT）家族在其行为和淀粉样变性表型中的作用。在这项研究中，我们进一步表征MT-1的作用，通过交叉Mt 1过表达小鼠与Tg 2576小鼠（APPTgMT）。在14个月大的小鼠中，MT-1（/2）蛋白水平因整个皮质（Cx）和海马（HC）的MT 1过表达而显着增加，皮质（Cx）和海马（HC）表现出明显的尾吻梯度。对照组雄性小鼠的淀粉样蛋白斑块周围区域MT-1（/2）免疫染色有增加的趋势，但Mt 1过表达小鼠中没有。淀粉样斑块引起神经胶质增生，但Mt 1过表达的影响是适度的。然而，在海马蛋白质印迹中，与APP野生型（APPWT）小鼠相比，老年雄性APPTgMT小鼠中的小胶质细胞标记物Iba-1增加，而在年轻小鼠中观察到相反的情况。在Tg 2576小鼠中观察到海马CA 1神经元损失，但不受Mt 1过表达的影响。老龄化增加锌和铜水平不同，这取决于大脑区域，性别和基因型。因此，Mt 1过表达对Tg 2576小鼠表型的影响是适度的。
The mouse model of Alzheimer’s disease (AD), Tg2576 mice (APP), has provided valuable information, such as the role of the metallothionein (MT) family in their behavioral and amyloidosis phenotypes. In this study, we further characterize the role of MT-1 by crossing Mt1-overexpressing mice with Tg2576 mice (APPTgMT). In 14-month-old mice, MT-1(/2) protein levels were dramatically increased by Mt1 overexpression throughout the cortex (Cx), which showed a prominent caudal-rostral gradient, and the hippocampus (HC). There was a trend for MT-1(/2) immunostaining to be increased in the areas surrounding the amyloid plaques in control male mice but not in Mt1-overexpressing mice. Gliosis was elicited by the amyloid plaques, but the effects of Mt1 overexpression were modest. However, in hippocampal western blots the microglial marker Iba-1 was increased in old male APPTgMT mice compared to APP-wild type (APPWT) mice, and the opposite was observed in young mice. Hippocampal CA1 neuronal loss was observed in Tg2576 mice, but was unaffected by Mt1 overexpression. Aging increased Zn and Cu levels differently depending on brain area, sex, and genotype. Thus, the effects of Mt1 overexpression on the phenotype of Tg2576 mice here studied are modest.