经颅交流电刺激对阿尔兹海默病小鼠双侧海马有效连接的干预研究

Intervention Study of Transcranial Alternating Current Stimulation on Bilateral Hippocampal Effective Connectivity in Alzheimer’s Disease Mice

通过格兰杰因果方法,对Y迷宫任务中双侧海马间的有效连接进行分析,从相连脑区的角度,研究经颅交流电刺激(tACS)干预阿尔兹海默症(AD)的神经机制。记录正常对照组、AD组、tACS组和假刺激组小鼠执行任务时的行为表现和海马左、右侧场电位,计算各组的功率谱密度和格兰杰因果值(GC)。研究发现:AD组行为训练的正确率低于正常对照组,tACS可以提高其正确率。在θ和γ频段上,AD组的功率谱密度显著低于正常对照组(P<0.01),tACS组接近正常对照组水平。在θ频段上,tACS增加了AD小鼠海马左侧到右侧和右侧到左侧异常的GC值(从0.111±0.002;0.109±0.003到0.377±0.017;0.185±0.005),和正常对照组接近;在γ频段上,tACS降低了AD小鼠海马左侧到右侧和右侧到左侧异常的GC值(从0.145±0.002;0.127±0.003到0.074±0.001;0.082±0.002),和正常对照组接近。双侧海马间有效连接的异常可能是AD小鼠记忆功能下降的原因,tACS可以改善海马间的异常连接且恢复海马处场电位的功率谱密度。

The effective connectivity in bilateral hippocampus during the Y maze task was analyzed with Granger causality method and the neural mechanism of transcranial alternating current stimulation(tACS)intervention in Alzheimer’s disease(AD)was studied from the perspective of connecting brain regions.The mice were divided into four groups:the normal control group,AD group,tACS stimulation group and sham stimulation group.The behavior performance and local field potentials in left and right hippocampus in four groups were recorded during the Y-maze working memory task.Power spectral density in four groups was compared.The Granger causality analysis value(GC)between the left and right hippocampus in four groups was analyzed.The correct rate of behavior training in AD group is lower than that of the normal control group,and tACS can increase the correct rate.In both θ and γ bands,power spectral density in AD group is remarkably lower than that in normal control group(P<0.01),while power spectral density in tACS stimulation group is improved to the level of normal control group.In the θ band,tACS stimulation can increase the abnormal GC value of AD mice hippocampus from left hippocampus to right hippocampus and right hippocampus to left hippocampus(from 0.111±0.002;0.109±0.003 to 0.377±0.017;0.185±0.005),which is close to the normal control group.In the γ band,tACS can reduce abnormal GC values between the left and right hippocampus in AD mice(from 0.145±0.002;0.127±0.003 to 0.074±0.001;0.082±0.002)and approach the levels of normal control group.This study illustrates the abnormal effective connectivity between the left and right hippocampus cause the decline in memory of Alzheimer’s mice.tACS can improve in the abnormal brain network connectivity between the bilateral hippocampus and in power spectral density in AD mice.