母子分离对青年CD-1雄鼠认知功能及海马BDNF介导的LTP的影响

Effects of maternal separation on cognitive function and BDNF-induced LTP of hippocampus in young CD-1 male mice

目的探究海马脑源性神经营养因子(BDNF)介导的长时程增强(LTP)是否参与母子分离(MS)导致子雄鼠青年期认知功能受损的过程。方法新生CD-1雄鼠随机分为母子分离组(MS组)和对照组(CON组),其中,MS组小鼠从出生后第4~21天每日与母鼠分开3 h,CON组不进行任何干预。两组小鼠在3月龄时用Morris水迷宫实验检测子鼠空间学习记忆能力,Western blot和RT-PCR检测子鼠海马BDNF表达水平,电生理技术检测海马CA3-CA1通路的LTP。结果与对照组相比,MS组学习期潜伏期及游泳路程均延长(P<0.01),记忆期靶象限时间及路程百分比均减少(P<0.05)。同时MS组海马的BDNF表达水平下降(P<0.05)和CA3-CA1通路的LTP受损(P<0.01)。结论一定强度的母子分离操作可以损害青年CD-1雄鼠的认知功能,且可能与海马区BDNF表达水平下降及LTP受损有关。

Objective To explore whether long-term potentiation(LTP)induced by brain-derived neurotrophic factor(BDNF)of hippocampus is involved in the process of maternal separation(MS)leading to impaired cognitive function of offspring in adolescence.Methods The newborn CD-1 mice were randomly divided into maternal separation group(MS group)and control group(CON group).Mice in MS group were separated from the mother mice for 3 h every day from postnatal day 4 to 21 while no intervention was taken in the CON group.The spatial learning and memory ability was assessed using Morris water maze at the age of 3 months.Western blot and real-time quantitative PCR were used to detect the levels of BDNF and BDNF mRNA in the hippocampus.LTP of the hippocampal CA3-CA1 neural pathway was recorded using electrophysiological techniques.Results Compared with CON group,the latency and distance of Morris water maze in maternal separation group were significantly longer(P<0.01).The percentage of time and distance in target quadrant during the memory phase in MS group were obviously lower than those in control group(P<0.05).The results of WB and Real-time quantitative PCR in MS group showed that the levels of BDNF and BDNF mRNA in MS group apparently decreased(P<0.05).Compared with CON group,MS group showed a significantly lower LTP in CA3-CA1 neural pathway(P<0.01).Conclusion The certain intensity of maternal separation can impair learning and memory function in young CD-1 male mice,which may be associated with decreased expression of BDNF and impaired LTP in the hippocampus.