Jang Woo Young, Lee Bo-Ram, Jeong Jain, Sung Younghun, Choi Minjee, Song Park, Kim Hyerim, Jang Soyoung, Kim Hyunmin, Joo Kyung-Il, Lee Jeong-Woong, Choo Yeon Sik, Kim Eunjoo, Ryoo Zae Young
School of Life Science and Biotechnology, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701, Republic of Korea.
School of Life Science and Biotechnology, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701, Republic of Korea; Division of Nano & Energy Convergence Research, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 711-873, Republic of Korea.
Brain Res. 2017 Jan 1;1654(Pt A):55-65. doi: 10.1016/j.brainres.2016.09.003. Epub 2016 Sep 5.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by loss of memory and cognitive abilities. In AD, amyloid β (Aβ) protein aggregates in the brain of patients, forming amyloid plaques. Aβ plaques are known to be surrounded by activated microglial cells. Serum amyloid A (SAA) is elevated from several hundred to 1000-fold as part of the immune response against various injuries, including trauma, infection, and inflammation. Additionally, continuous elevation of SAA is related to the development of amyloidosis. This study was designed to identify the relationship between SAA1 and AD using liver specific SAA1 overexpressing mice (TG), because SAA1 is expressed in the liver during the acute phase. We detected exogenous SAA1 expression in the brain of TG mice. This result implies that liver-derived SAA1 migrates to the brain tissues. Thus, we confirmed that the blood brain barrier (BBB) functioned normally using Evans-blue staining and CARS. Furthermore, our results show an increase in the accumulation of the 87kDa form of Aβ in TG mice compared to wild type mice (WT). Additionally, the number of microglial cells and levels of pro-inflammatory cytokines were increased. Next, we investigated the relationship between SAA1 and depression by performing social interaction tests. The results showed that TG mice have a tendency to avoid stranger mice and an impaired social recognition. In conclusion, the SAA1 TG mouse model is a valuable model to study depression.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征为记忆和认知能力丧失。在AD患者中，淀粉样β（Aβ）蛋白在大脑中聚集，形成淀粉样斑块。已知Aβ斑块被活化的小胶质细胞包围。血清淀粉样蛋白A（SAA）作为针对包括创伤、感染和炎症在内的各种损伤的免疫反应的一部分，会从几百倍升高到1000倍。此外，SAA的持续升高与淀粉样变性的发展有关。本研究旨在利用肝脏特异性过表达SAA1的小鼠（TG）来确定SAA1与AD之间的关系，因为SAA1在急性期在肝脏中表达。我们在TG小鼠的大脑中检测到了外源性SAA1的表达。这一结果表明肝脏来源的SAA1迁移到了脑组织中。因此，我们通过伊文思蓝染色和相干反斯托克斯拉曼散射（CARS）证实血脑屏障（BBB）功能正常。此外，我们的结果显示，与野生型小鼠（WT）相比，TG小鼠中87kDa形式的Aβ积累增加。此外，小胶质细胞数量和促炎细胞因子水平也增加了。接下来，我们通过进行社会互动测试来研究SAA1与抑郁之间的关系。结果显示，TG小鼠有避开陌生小鼠的倾向，且社会识别能力受损。总之，SAA1 TG小鼠模型是研究抑郁的一个有价值的模型。
