海马内注射Aβ1-42寡聚体影响大鼠焦虑、抑郁行为及突触可塑性  

Intrahippocampal injection of Aβ1-42 affects the anxiety,depression and hippocampal synaptic plasticity in rats

作　　者：张洋[1] 原丽[1] 张军[1] 张升校 祁金顺[1] 

机构地区：[1]山西医科大学生理学系,太原030001

出　　处：《神经解剖学杂志》2014年第4期431-436,共6页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(31271201);山西省自然科学基金(2010011049-3)

摘　　要：目的:探讨淀粉样β蛋白(Aβ)对大鼠焦虑和抑郁行为的影响及其可能的突触机制。方法:将SD大鼠随机分为对照组(n=10)和Aβ1-42注射组(n=10)。通过联合采用高架十字迷宫、强迫游泳及电生理实验技术,以动物在迷宫开臂和闭臂中停留时间百分比、在强迫游泳中的不动时间以及在体海马场兴奋性突触后电位(fEPSP)的幅度作为主要观察指标,系统研究了海马内注射Aβ1-42寡聚体对大鼠焦虑、抑郁行为及海马突触可塑性的影响。结果:(1)Aβ1-42组大鼠在高架十字迷宫开臂中所停留的时间百分比明显大于正常组(P<0.01),在闭臂中停留的时间百分比则明显小于对照组(P<0.01);(2)Aβ1-42组大鼠在强迫游泳测试中"不动"时间较对照组明显增加(P<0.01),"游泳"时间则明显减少(P<0.05);(3)高频刺激(HFS)后Aβ1-42组大鼠的海马LTP受到明显压抑,HFS后即刻以及HFS后30 min和60 min时fEPSP平均幅度均明显下降(P<0.05或P<0.01)。结论:海马内注射Aβ可导致大鼠行为脱抑制、引起抑郁样行为并伤害突触可塑性,提示海马LTP的异常不仅影响学习记忆功能,可能也与焦虑和抑郁等精神行为异常的发生有关。Objective： To explore the effect of amyloid β protein （Aβ）on anxiety and depression-related behaviors and its possible synaptic mechanism. Methods： SD rats were randomly divided into control （n = 10）and Aβ1-42 （n = 10） groups. By using elevated plus-maze, forced swimming and in vivo electrophysiological techniques, we investigated the effect of intrahippocampal injection of Aβ1- 42 oligomer on the anxiety, depression and hippoeampal synaptie plasticity. The main observation parameters include the time percentage of rats spending in the open arms or closed arms in elevated plus-maze, the mean times of immobility in forced swimming test, and the amplitudes of fEPSP in hippocampal CA1 region of rats. Results： （ 1 ） The time percentage of rats in open arms was significantly higher and the time percentage in closed arms was lower in Aβ1-42 group than in control group （P 〈 0. 01 ） ; （2） The mean time of immobility of rats was significantly increased （P 〈 0.01 ）, and the mean swimming time was decrease （P 〈 0.05 ） in Aβ1-42 group compared to the control group. （ 3 ） Intrahippoeampal injection of Aβ1- 42 significantly suppressed HFS-induced hippoeampal LTP （ P 〈 0.01 ;P 〈 0.01 ）, with decreased amplitude of fEPSP at 30rain and 60rain after HFS. Conclusion： These results indicated that Aβ can induce behavioral disinhibition and suppression in rats, suggesting that the impairment of syna pticplasticity may be involved in these behavioral disorders happened in AD.

关 键 词：淀粉样Β蛋白 行为脱抑制 抑郁 海马长时程增强 

分 类 号：R749.4[医药卫生—神经病学与精神病学] R749.72[医药卫生—临床医学]