Luo Yinpei, Yang Wenjuan, Li Nian, Yang Xiufang, Zhu Binglian, Wang Cong, Hou Wensheng, Wang Xing, Wen Huizhong, Tian Xuelong
Chongqing Engineering Research Center for Medical Electronics Technology, Bioengineering College, Chongqing University, Chongqing, China.
College of Microelectronics and Communication Engineering, Chongqing University, Chongqing, China.
Front Aging Neurosci. 2020 May 13;12:134. doi: 10.3389/fnagi.2020.00134. eCollection 2020.
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 β-amyloid (Aβ), 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 Aβ 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 Aβ or directly affecting production and degradation of Aβ to reduce glial activation. AtDCS is an effective means of early intervention in the early stage of AD.
阿尔茨海默病（AD）是一种不可逆的进行性神经退行性疾病。对AD早期进行干预是目前正在探索的AD治疗新途径。基于我们之前的研究，对淀粉样前体蛋白（APP）/早老素-1（PS1）转基因小鼠这一AD小鼠模型早期进行阳极经颅直流电刺激（AtDCS）的行为和病理影响展开了研究。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治疗。采用莫里斯水迷宫（MWM）任务和新物体识别（NOR）任务来测试小鼠的记忆力。对β-淀粉样蛋白（Aβ）、胶质纤维酸性蛋白（GFAP）和神经丝蛋白200（NF200）进行尼氏染色、蛋白质免疫印迹法（WB）、免疫组织化学和免疫荧光染色以进行病理分析。在MWM中，ADT组和CTL组的逃避潜伏期比AD组和ADST组短，穿越平台区域的次数更多。在NOR任务中，各组之间的辨别指数无显著差异。病理分析显示AD组和ADT组之间存在明显差异。本研究表明，早期APP/PS1转基因小鼠未表现出识别记忆障碍。AtDCS有效改善了AD早期APP/PS1转基因小鼠模型的空间学习和记忆能力，减轻了Aβ负担，并对神经元具有保护作用。AtDCS可通过激活许多胶质细胞来促进Aβ的降解和清除，或直接影响Aβ的产生和降解以减少胶质细胞激活，从而改善AD相关症状。AtDCS是AD早期干预的有效手段。
