中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (10): 2278-2285.doi: 10.4103/1673-5374.337053

• 原著:退行性病与再生 • 上一篇    下一篇

经颅直流电刺激干预可长期改善阿尔茨海默病临床前阶段APP/PS1小鼠的认知障碍

  

  • 出版日期:2022-10-15 发布日期:2022-03-16
  • 基金资助:
    中国国家自然科学基金项目(31971287);陆军医科大学基础医学院高等学科交叉研究基金项目(2018JCQY07)

Anodal transcranial direct current stimulation alleviates cognitive impairment in an APP/PS1 model of Alzheimer’s disease in the preclinical stage

Yin-Pei Luo1, 2, Zhi Liu3, Cong Wang2, Xiu-Fang Yang2, Xiao-Ying Wu2, Xue-Long Tian2, Hui-Zhong Wen1   

  1. 1Chongqing Key Laboratory of Neurobiology, Department of Neurobiology, School of Basic Medicine, Army Medical University, Chongqing, China; 2Chongqing Medical Electronics Engineering Technology Research Center, Laboratory of Neural Regulation and Rehabilitation Technology, College of Bioengineering, Chongqing University, Chongqing, China; 3Department of Histology and Embryology, School of Basic Medicine, Army Medical University, Chongqing, China
  • Online:2022-10-15 Published:2022-03-16
  • Contact: Hui-Zhong Wen, PhD, justzhong@sina.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 31971287 (to XYW) and the Advanced Interdisciplinary Studies Foundation of School of Basic Medical Science, Army Medical University of China, No. 2018JCQY07 (to HZW).

摘要:

经颅直流电刺激已被证明可在临床前阶段改善阿尔茨海默病的记忆和认知功能,但既往研究仅在刺激后即刻进行检测,其长期影响尚不可知。实验对处于阿尔茨海默病临床前阶段的鼠龄为26周APP/PS1小鼠进行10次经颅直流电刺激或假刺激。治疗后6周,与接受假刺激的小鼠相比,经颅直流电刺激的小鼠在Morris水迷宫测试中逃逸潜伏期和路径更短,越过平台的次数更多,在目标象限中停留的时间更长;在新物体识别和新物体定位测试中辨别率和定位指数更高。同时经颅直流电刺激还能降低小鼠海马组织中Aβ42和星形胶质细胞活化的标志物胶质纤维酸性蛋白水平,并增加神经元标志物NeuN 水平。表明经颅直流电刺激可改善APP/PS1小鼠在临床前阶段的学习记忆和组织病理状态,且其效果至少持续了6周。

https://orcid.org/0000-0001-5590-4275 (Hui-Zhong Wen); https://orcid.org/0000-0002-2971-7529 (Xue-Long Tian)

关键词: 经颅直流电刺激, 临床前阶段, 阿尔茨海默病, 长期影响, 认知功能, 神经元, 淀粉样蛋白β, 炎症

Abstract: Anodal transcranial direct current stimulation (AtDCS) has been shown to alleviate cognitive impairment in an APP/PS1 model of Alzheimer’s disease in the preclinical stage. However, this enhancement was only observed immediately after AtDCS, and the long-term effect of AtDCS remains unknown. In this study, we treated 26-week-old mouse models of Alzheimer’s disease in the preclinical stage with 10 AtDCS sessions or sham stimulation. The Morris water maze, novel object recognition task, and novel object location test were implemented to evaluate spatial learning memory and recognition memory of mice. Western blotting was used to detect the relevant protein content. Morphological changes were observed using immunohistochemistry and immunofluorescence staining. Six weeks after treatment, the mice subjected to AtDCS sessions had a shorter escape latency, a shorter path length, more platform area crossings, and spent more time in the target quadrant than sham-stimulated mice. The mice subjected to AtDCS sessions also performed better in the novel object recognition and novel object location tests than sham-stimulated mice. Furthermore, AtDCS reduced the levels of amyloid-β42 and glial fibrillary acidic protein, a marker of astrocyte activation, and increased the level of neuronal marker NeuN in hippocampal tissue. These findings suggest that AtDCS can improve the spatial learning and memory abilities and pathological state of an APP/PS1 mouse model of Alzheimer’s disease in the preclinical stage, with improvements that last for at least 6 weeks.

Key words: Alzheimer’s disease, amyloid-β, anodal transcranial direct current stimulation, cognitive function, inflammation, long-term effect, neuron, preclinical stage