慢性应激对大鼠认知及小胶质细胞Aβ沉积的影响  

Effects of chronic stimulation on cognition and Aβ deposition of microglia in rats

作　　者：黄丽 吕霞 樊珺婷 马泽微 张美琳[1,2] 刘欢 HUANG Li;LV Xia;FAN Junting(School of Public Health,Tianjin Medical University,Tianjin 300070,China)

机构地区：[1]天津医科大学公共卫生学院,天津市300070 [2]天津市环境营养与人群健康重点实验室

出　　处：《精神医学杂志》2022年第2期130-134,共5页Journal of Psychiatry

基　　金：国家自然科学基金项目(编号:82173516);天津市教委科研计划项目(编号:2019ZD026)。

摘　　要：目的 观察慢性应激对大鼠认知功能和小胶质细胞β-淀粉样蛋白(Aβ)沉积的影响。方法 16只雄性SD大鼠,随机分为模型组和对照组各8只。模型组大鼠经历12周慢性不可预知性刺激(CUMS),对两组大鼠进行行为学检测,检测脑组织Aβ和Aβ含量及其在小胶质细胞中沉积情况,检测小胶质细胞内Toll样受体4(TLR4)和晚期糖基化终产物受体(RAGE)的表达。结果 与对照组比较,模型组旷场实验和高架十字迷宫实验中的静止时间增加(P<0.01),运动距离缩短(P<0.05);模型组大鼠脑内Aβ和Aβ水平均升高(P<0.05);模型组大鼠海马区和皮质区活化的小胶质细胞的数量增加(P<0.05);模型组大鼠海马区和皮质区中小胶质细胞内的Aβ和Aβ增加(P<0.05);海马和皮质区内的小胶质细胞内TLR4和RAGE表达增加(P<0.05)。结论 慢性应激可引起大鼠认知功能减退,促进小胶质细胞激活和Aβ摄取受体表达上调,使小胶质细胞内Aβ含量增加。Objective To observe the effects of chronic stimulation on cognitive function and Aβ deposition of microglia in rats. Methods A total of 16 male SD rats were randomly divided into control group(8 cases) and model group(8 cases). The rats in model group experienced 12 weeks CUMS stimulation. At the end of the 12week, the behavior experiments were conducted, and levels of Aβand Aβ,as well as their concentrations in microglia were tested. Expressions of TLR4 and RAGE in microglia were also tested.Results Compared with control group, the immobility times in model group in open field test and elevated plus-maze test were increased(P<0.01), and the distances were decreased(P<0.05). After CUMS stimulation, levels of Aβand Aβin brain were significantly increased, and microglia was activated in hippocampus and cortical area(P<0.05). Concentrations of Aβand Aβ, as well as expressions of TLR4 and RAGE in microglia in hippocampus and cortical area of model group were increased(P<0.05). Conclusion Chronic stimulation induces cognitive decline in rats, improves the microglia activation, up-regulates Aβ uptake receptors and increases the concentration of Aβ in microglia.

关 键 词：慢性应激 小胶质细胞 认知功能 AΒ 

分 类 号：R749[医药卫生—神经病学与精神病学]