Comparative Studies on Behavioral, Cognitive and Biomolecular Profiling of ICR, C57BL/6 and Its Sub-Strains Suitable for Scopolamine-Induced Amnesic Models
Comparative Studies on Behavioral, Cognitive and Biomolecular Profiling of ICR, C57BL/6 and Its Sub-Strains Suitable for Scopolamine-Induced Amnesic Models
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DOI：
10.3390/ijms18081735
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发表时间：
2017-08-01
影响因子：
5.6
通讯作者：
Choi, Dong-Kug
中科院分区：
文献类型：
--
作者：
Karthivashan, Govindarajan;Park, Shin-Young;Choi, Dong-Kug
认知障碍和行为差异是大多数神经退行性疾病动物模型中需要研究的独特基线特征。然而，神经元并发症是多因素的，需要合适的动物模型来研究其潜在的基础机制。相比之下，现有的许多神经退行性研究都利用了不同的动物品系，导致了事实差异。因此，选择最佳的小鼠品系来初步评估神经元并发症势在必行。在这项研究中，我们系统地比较了东莨菪碱引起的遗忘症的远交 ICR 和近交 C57BL/6 小鼠品系的行为、认知、胆碱能和炎症损伤。然后，我们将这项研究扩展到亚株C57BL/6N和C57BL/6J，除了上述参数外，还评估了它们的内源抗氧化剂水平和cAMP反应元件结合蛋白（CREB）/脑源性神经营养因子（BDNF）蛋白表达。与 ICR 菌株相比，受东莨菪碱影响的 C57BL/6 菌株表现出自发交替的显着减少，并且与对照组相比，炎症蛋白表达增加了约两倍。在亚菌株中，与对照组和他克林处理组相比，东莨菪碱处理的 C57BL/6N 菌株表现出步进潜伏期缩短、乙酰胆碱酯酶 (AChE) 活性和炎症蛋白表达升高，与内源性抗氧化剂水平和 p-CREB/BDNF 表达降低相关。这表明与其他评估菌株相比，C57BL/6N 菌株表现出显着增强的东莨菪碱诱导的神经元损伤。
Cognitive impairment and behavioral disparities are the distinctive baseline features to investigate in most animal models of neurodegenerative disease. However, neuronal complications are multifactorial and demand a suitable animal model to investigate their underlying basal mechanisms. By contrast, the numerous existing neurodegenerative studies have utilized various animal strains, leading to factual disparity. Choosing an optimal mouse strain for preliminary assessment of neuronal complications is therefore imperative. In this study, we systematically compared the behavioral, cognitive, cholinergic, and inflammatory impairments of outbred ICR and inbred C57BL/6 mice strains subject to scopolamine-induced amnesia. We then extended this study to the sub-strains C57BL/6N and C57BL/6J, where in addition to the above-mentioned parameters, their endogenous antioxidant levels and cAMP response-element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) protein expression were also evaluated. Compared with the ICR strain, the scopolamine-inflicted C57BL/6 strains exhibited a substantial reduction of spontaneous alternation and an approximately two-fold increase in inflammatory protein expression, compared to the control group. Among the sub-strains, scopolamine-treated C57BL/6N strains exhibited declined step-through latency, elevated acetylcholinesterase (AChE) activity and inflammatory protein expression, associated with reduced endogenous antioxidant levels and p-CREB/BDNF expression, compared to the control and tacrine-treated groups. This indicates that the C57BL/6N strains exhibit significantly enhanced scopolamine-induced neuronal impairment compared to the other evaluated strains.