Saa3缺失改善阿尔茨海默病模型小鼠认知功能障碍和Tau蛋白病理进展

陈岩青; 宫平; 刘震; 张岩; 于洋

doi:10.11665/j.issn.1000-5048.20210511

Saa3缺失改善阿尔茨海默病模型小鼠认知功能障碍和Tau蛋白病理进展

上海交通大学药学院，上海 200240

基金项目: 国家自然科学基金资助项目（No.81870835，No.81571027）

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出版历程
- 收稿日期: 2021-02-03
- 修回日期: 2021-09-11
- 刊出日期: 2021-10-24

Serum amyloid A 3 deficiency improves cognitive impairment and attenuates tau pathology in mouse model of Alzheimer′s disease

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China

Funds: This study was supported by the National Natural Science Foundation of China (No. 81870835, No.81571027)

摘要

摘要: 探究血清淀粉样蛋白A（serum amyloid A， SAA）对阿尔茨海默病（Alzheimer′s disease，AD）模型小鼠的认知功能及tau蛋白磷酸化水平的影响。构建Saa3缺失的APP/PS1转基因AD小鼠模型和侧脑室内（ICV）注射链脲佐菌素（STZ）AD小鼠模型。采用免疫荧光方法检测两种AD模型小鼠脑内Saa3的表达。记录ICV注射STZ小鼠造模期间的体重变化。采用转棒式疲劳仪、旷场实验和高架十字迷宫分别检测小鼠运动协调和平衡能力、自主运动能力和焦虑程度。Morris水迷宫实验评估小鼠的空间学习和记忆能力。Western blot实验检测小鼠脑组织中tau蛋白的磷酸化水平。结果发现，两种AD模型小鼠脑内Saa3的表达显著增加。Saa3缺失对两种AD模型小鼠的运动协调和平衡能力及自主运动能力无显著影响。Saa3缺失缓解了AD小鼠的焦虑程度。Saa3缺失改善了ICV注射STZ模型小鼠和APP/PS1小鼠的学习和记忆能力损伤。Saa3缺失降低了AD小鼠脑内tau蛋白特定位点的磷酸化水平。组间差异有统计学意义（P < 0.05）。这些结果表明，Saa3参与AD的认知功能和tau蛋白的病理进展，抑制SAA为AD的治疗和预防提供了新策略。
- 血清淀粉样蛋白A /
- 阿尔茨海默病 /
- tau蛋白磷酸化 /
- Morris水迷宫
Abstract: To explore the effects of serum amyloid A (SAA) on the cognitive function and tau phosphorylation in Alzheimer''s disease (AD), two mouse models of AD were constructed: one is the APP/PS1 double transgenic mice mated with the Saa3 knockout (Saa3^-/-) mice, and the other involves intracerebroventricular (ICV) injection of streptozotocin (STZ) into WT and Saa3^-/- mice.The expression of Saa3 in mouse brain was evaluated using immunofluorescence staining.The body weight of STZ injection mice during modeling was measured.The motor coordination and balance, spontaneous exploratory activity, and anxiety level of these mice were assessed by Rotarod test, open field, and elevated plus maze, respectively.Spatial reference learning and memory were evaluated by Morris water maze.Western blot was used to detect the phosphorylation level of tau protein in mouse brain tissue.The results showed that the expression of Saa3 was increased in the brain of AD mice.The Saa3 gene deletion had no significant effect on motor coordination, balance and spontaneous exploratory activity in these mice, yet with alleviated anxiety level of AD model mice.Saa3 deficiency improved the impairment of learning and memory function of intracerebroventricular STZ injection mice and APP/PS1 mice. Deletion of Saa3 relieved the hyperphosphorylation of tau protein at specific sites in the brain of AD mice. The difference between the groups was statistically significant (P < 0.05). These results suggest that Saa3 is associated with cognitive function and tau pathology in AD, and that the inhibition of SAA may be a new strategy for the treatment of AD.
- serum amyloid A /
- Alzheimer''s Disease /
- Tau phosphorylation /
- Morris water maze

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Saa3缺失改善阿尔茨海默病模型小鼠认知功能障碍和Tau蛋白病理进展

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Serum amyloid A 3 deficiency improves cognitive impairment and attenuates tau pathology in mouse model of Alzheimer′s disease

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