脂联素改善阿尔茨海默病模型小鼠焦虑情绪及工作记忆  

Effects of adiponectin on the anxiety and memory impairment in triple transgenic Alzheimer's disease model mice

作　　者：曲雪松[1] 石辉[1,2] 曹秀丽 董雪帆[1] 李甜 焦娟娟[1] 祁金顺[1] 武美娜[1] 

机构地区：[1]山西医科大学生理学系细胞生理学省部共建教育部重点实验室,太原030001 [2]内蒙古赤峰市医院重症医学科,赤峰024000

出　　处：《中国应用生理学杂志》2017年第5期405-409,共5页Chinese Journal of Applied Physiology

基　　金：国家自然科学基金(31300968);青年三晋学者支持计划专项经费资助

摘　　要：目的:探讨脂联素(APN)预处理对9月龄三转基因阿尔茨海默病(3xTg-AD)模型小鼠学习记忆能力和焦虑情绪的影响。方法:选取9月龄3xTg-AD小鼠及C57BL/6J小鼠,分为4组:WT+Saline组、3xTg-AD+Saline组、WT+APN组和3xTg-AD+APN组,每组8只。将全部小鼠进行侧脑室埋管术后,恢复7 d,在自由清醒状态下分别经侧脑室给予生理盐水或APN,采用旷场、新物体识别及Y-迷宫3种行为学手段检测小鼠的情绪及学习记忆能力。结果:(1)在旷场实验中,与WT+Saline组小鼠相比,3xTg-AD+Saline组小鼠在中央区域的活动时间明显缩短,在外周区域的活动时间明显延长,给予APN后可有效逆转3xTg-AD小鼠的该现象,表明脂联素可有效缓解3xTg-AD小鼠的焦虑情绪。(2)新物体识别实验中,3xTg-AD+Saline组小鼠的辨别指数为(-16.7±10.1)%,明显低于WT+Saline组的(18.0±8.2)%(P<0.01)和3xTg-AD+APN组的(15.7±8.8)%(P<0.01),表明脂联素可明显改善3xTg-AD小鼠的识别记忆能力损伤。(3)Y-迷宫实验中,3xTg-AD+Saline组小鼠的自发交替正确率为(40.0±1.7)%,明显低于WT+Saline组的(56.6±4.6)%(P<0.01)和3xTg-AD+APN组的(53.9±5.6)%(P<0.01),表明脂联素能够逆转3xTg-AD小鼠工作记忆能力的损伤。结论:脂联素可以改善9月龄3xTg-AD小鼠的焦虑情绪及识别记忆和工作记忆能力损伤,可能在AD的预防和治疗中发挥有效作用。Objective： To investigate the effects of adiponectin （APN） on anxiety and memory impairment of 9-month-old triple transgenic Alzheimer＇ s disease （3xTg-AD） model mice. Methods： The 9-month-old 3xTg-AD mice and C57BL/6J mice were randomly divided into four groups （n=8 for each group）： Wild type（WT） ＋ Saline, 3xTg-AD ＋ Saline, WT ＋ APN and 3xTg-AD ＋ APN group. All mice were im- planted cannula in lateral ventricle and each mouse was intracerebroventricular injected with adiponectin or saline under free moving condition after 7 days recovery. The anxiety and memory ability of each mouse were observed by using open field test, object recognition task and Y- maze test. Results： OIn the open field test, compared to WT ＋ Saline group, the time of 3xTg-AD ＋ Saline mice spent in center was significandy decreased, and the time spent in periphery was obviously increased. However, APN treatment effectively reversed the phenomenon appeared in 3xTg-AD mice, indicating that APN could alleviate the anxiety observed in 3xTg-AD mice. QIn novel object recognition task, the discrimination index of 3xTg-AD ＋ Saline group was （-16.7 ± 10.1 ） %, significantly lower than （ 18.0 ± 8.2） % in WT ＋ Saline group （ P 〈 0.01 ） and （ 15.7 ± 8.8） % in 3xTg-AD ＋ APN group （ P 〈 0.01 ）, which indicated that APN could effectively prevent the recognition memory impairment in 3xTg mice. QIn Y-maze test, the spontaneous alternation rate of 3xTg-AD ＋ Saline group was （40.0 ±1.7） %, significantly lower than （56.6±4.6）% in WT ＋ Saline group and （53.9± 5.6）% in 3xTg-AD ＋ APN group （ P 〈 0.01）, which indicated that APN could prevent working memory impairment in 3xTg-AD mice. Conclusion： Adiponectin could effectively alleviate the anxiety and reverse the impairment of recognition memory and working memory of 9-month-old 3xTg-AD mice, and might play an important role in the prevention and treatment of AD.

关 键 词：脂联素 阿尔茨海默病 三转基因小鼠 焦虑 学习记忆 

分 类 号：R338[医药卫生—人体生理学]