Anodal Transcranial Direct Current Stimulation Can Improve Spatial Learning and Memory and Attenuate Aβ42Burden at the Early Stage of Alzheimer's Disease in APP/PS1 Transgenic Mice
Anodal Transcranial Direct Current Stimulation Can Improve Spatial Learning and Memory and Attenuate Aβ42Burden at the Early Stage of Alzheimer's Disease in APP/PS1 Transgenic Mice
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阳极经颅直流电刺激可改善 APP/PS1 转基因小鼠的空间学习和记忆并减轻阿尔茨海默氏病早期的 A beta(42) 负担
DOI：
10.3389/fnagi.2020.00134
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发表时间：
2020-05-13
影响因子：
4.8
通讯作者：
Tian, Xuelong
中科院分区：
文献类型：
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作者：
Luo, Yinpei;Yang, Wenjuan;Tian, Xuelong
阿尔茨海默病（AD）是一种不可逆的进行性神经退行性疾病。早期干预是阿尔茨海默病治疗的新途径，正在探索中。我们在前期研究的基础上，研究了经颅直流电刺激（AtDCS）对AD早期小鼠模型，即淀粉样蛋白前体蛋白(APP)/早老素-1 （PS1）转基因小鼠的行为和病理影响。将33只6月龄雄性APP/PS1小鼠随机分为模型组（AD组）、模型+假刺激组（ADST组）和刺激组（ADT组）。随机选取11只6月龄雄性C57野生型小鼠作为对照组（CTL组）。ADT组接受10次AtDCS会话。采用Morris水迷宫（MWM）任务和新物体识别（NOR）任务测试小鼠记忆。对β -淀粉样蛋白（A β(42)）、胶质纤维酸性蛋白（GFAP）、NF200进行尼氏染色、Western blot （WB）、免疫组化和免疫荧光染色进行病理分析。在MWM中，ADT组和CTL组比AD组和ADST组有更短的逃避潜伏期和更多的平台-区域交叉。在NOR任务中，各组间的辨别指数无显著差异。病理分析显示AD组与ADT组有明显差异。本研究发现，早期APP/PS1转基因小鼠未出现识别记忆障碍。AtDCS有效改善早期APP/PS1转基因AD小鼠模型的空间学习记忆，减轻A β负担，对神经元具有保护作用。AtDCS可通过激活许多胶质细胞促进A β的降解和清除或直接影响A β的产生和降解来减少胶质细胞的活化，从而改善ad相关症状。AtDCS是AD早期早期干预的有效手段。
Alzheimer's disease (AD) is an irreversible progressive neurodegenerative disease. Intervention in the early stage of AD is a new path for AD treatment that is being explored. The behavioral and pathological effects of anodal transcranial direct current stimulation (AtDCS) at the early stage of AD in the mouse model, amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, were investigated based on our previous studies. Thirty-three 6-month-old male APP/PS1 mice were randomly divided into the model group (AD group), model + sham stimulation group (ADST group) and stimulation group (ADT group). Eleven 6-month-old male C57 wild-type mice were randomly selected as a control group (CTL group). The ADT group received 10 AtDCS sessions. The Morris water maze (MWM) task and novel object recognition (NOR) task were used to test mouse memory. Nissl staining, Western blot (WB), immunohistochemistry and immunofluorescence staining of beta-amyloid (A beta(42)), glial fibrillary acidic protein (GFAP) and NF200 were conducted for pathological analysis. The ADT group and the CTL group had a shorter escape latency and more platform-region crossings than the AD group and ADST group in the MWM. There was no significant difference in the discrimination index among the groups in the NOR task. Pathological analysis showed visible differences between the AD group and ADT group. This study revealed that early-stage APP/PS1 transgenic mice did not show recognition memory impairment. AtDCS effectively improved spatial learning and memory in the early-stage APP/PS1 transgenic mouse model of AD, alleviating A beta burden and having a protective effect on neurons. AtDCS could improve AD-related symptoms by activating many glial cells to promote the degradation and clearance of A beta or directly affecting production and degradation of A beta to reduce glial activation. AtDCS is an effective means of early intervention in the early stage of AD.