Objective

To investigate the regulatory role of STC1 (Stanniocalcin-1) mediated ERK1/2 pathway in cognitive impairment and neuroinflammation of Alzheimer’s disease (AD).

Methods

WT mice and STC1 Tg mice (transgenic overexpression of STC1) were used to establish AD models to perform behavioral test by Morris water maze. Hippocampal cell apoptosis was quantified by TUNEL staining, the levels of inflammatory cytokines in serum and hippocampal tissues determined by ELISA, as well as oxidative stress-related factors detected by corresponding testing kits, and protein expression of STC1 and ERK1/2 pathway measured by Western blotting.

Results

Compared with WT Sham group, WT AD mice had prolonged escape latency, decreased crossing platform times, increased hippocampal cell apoptosis with up-regulated inflammatory cytokines and oxidative stress-related factors, as well as increased STC1 and ERK1/2 pathway-related molecules. By contrast, STC1 Tg AD mice showed shortened escape latency, increased crossing platform times than WT AD mice, and they also exhibited the decreased apoptosis index and inflammatory cytokines, alleviated oxidative stress-injury, down-regulated protein expression of ERK1/2 pathway, and up-regulated the protein expression of STC1 and UCP2.

Conclusion

STC1 overexpression could alleviate oxidative stress-induced injury, reduce neuroinflammation, improve cognitive function to play a neuro-protective role by inhibiting ERK1/2 signaling pathway.

中文翻译：

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STC1通过抑制ERK1/2通路改善阿尔茨海默病小鼠的认知障碍和神经炎症

客观的

研究 STC1 (Stanniocalcin-1) 介导的 ERK1/2 通路在阿尔茨海默病 (AD) 的认知障碍和神经炎症中的调节作用。

方法

WT小鼠和STC1 Tg小鼠（STC1的转基因过表达）用于建立AD模型，通过Morris水迷宫进行行为测试。TUNEL染色定量海马细胞凋亡，ELISA法检测血清和海马组织中炎性细胞因子水平，相应试剂盒检测氧化应激相关因子，Western检测STC1和ERK1/2通路蛋白表达印迹。

结果

与WT Sham组相比，WT AD小鼠逃逸潜伏期延长，跨平台时间减少，海马细胞凋亡增加，炎症细胞因子和氧化应激相关因子上调，STC1和ERK1/2通路相关分子增加。相比之下，STC1 Tg AD 小鼠比 WT AD 小鼠表现出缩短的逃逸潜伏期，增加跨平台时间，并且它们还表现出细胞凋亡指数和炎性细胞因子降低，减轻氧化应激损伤，下调 ERK1/2 通路的蛋白表达，并上调 STC1 和 UCP2 的蛋白表达。

结论

STC1过表达可通过抑制ERK1/2信号通路减轻氧化应激损伤、减轻神经炎症、改善认知功能发挥神经保护作用。