Anodal Transcranial Direct Current Stimulation Can Improve Spatial Learning and Memory and Attenuate Aβ42 Burden at the Early Stage of Alzheimer's Disease in APP/PS1 Transgenic Mice.

Yinpei Luo,Wenjuan Yang,Xuelong Tian,Cong Wang,Wensheng Hou,Binglian Zhu,Huizhong Wen,Xiufang Yang,Nian Li,Xing Wang

doi:10.3389/fnagi.2020.00134

Abstract

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 (Aβ42), 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.

Highlights

Alzheimer’s disease (AD) is a serious neurodegenerative disease characterized by cognitive and memory dysfunction (Cummings et al, 2014; Alzheimer’s Association, 2018)
All 11 amyloid precursor protein (APP)/PS1 transgenic mice in the ADT group were well treated with anodal transcranial direct current stimulation (AtDCS) and performed behavioral tasks with 33 other mice in the CTL, ADST, and AD groups
Among the four groups of mice, only the CTL and ADT groups exhibited significant differences between the time spent in the third quadrant and the time spent in the other quadrants (Figure 3G, the first, second, and fourth quadrant vs. the third quadrant: CTL, F(1,20) = 22.029, 16.904, 22.056, P < 0.001, =0.001,

Summary

Introduction

Alzheimer’s disease (AD) is a serious neurodegenerative disease characterized by cognitive and memory dysfunction (Cummings et al, 2014; Alzheimer’s Association, 2018). It has become the seventh leading cause of death in the world (Patterson, 2018). Based on the long preclinical stage and the irreversible characteristics of AD, the clinical stage of AD may not be the optimal period of treatment (Selkoe and Hardy, 2016). The National Institute on Aging and the Alzheimer’s Association divide preclinical AD into three phases (Sperling et al, 2011): Stage 1, asymptomatic cerebral amyloidosis; Stage 2, neuron degeneration; Stage 3, subtle cognitive/behavioral decline, which eventually evolves into AD with time. Intervention before AD diagnosis may delay or even prevent brain lesions, thereby significantly reducing the symptoms of patients with AD and the cost of aged care (McManus and Heneka, 2017; Alzheimer’s Association, 2018)

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