Modulation of Long-Term Potentiation by Gamma Frequency Transcranial Alternating Current Stimulation in Transgenic Mouse Models of Alzheimer's Disease.

Won-Hyeong Jeong,In-Sung Choi,Jae-Young Han,Wang-In Kim,Min-Keun Song,Hyeng-Kyu Park,Jin-Won Lee

doi:10.3390/brainsci11111532

Won-Hyeong Jeong, In-Sung Choi + Show 5 more

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https://doi.org/10.3390/brainsci11111532

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Journal: Brain sciences	Publication Date: Nov 19, 2021
Citations: 15	License type: CC BY 4.0

Affiliation: Chonnam National University Hospital

Abstract

Transcranial alternating current stimulation (tACS) is a neuromodulation procedure that is currently studied for the purpose of improving cognitive function in various diseases. A few studies have shown positive effects of tACS in Alzheimer’s disease (AD). However, the mechanism underlying tACS has not been established. The purpose of this study was to investigate the mechanism of tACS in five familial AD mutation (5xFAD) mouse models. We prepared twenty 4-month-old mice and divided them into four groups: wild-type mice without stimulation (WT-NT group), wild-type mice with tACS (WT-T group), 5xFAD mice without stimulation (AD-NT group), and 5xFAD mice with tACS (AD-T group). The protocol implemented was as follows: gamma frequency 200 μA over the bilateral frontal lobe for 20 min over 2 weeks. The following tests were conducted: excitatory postsynaptic potential (EPSP) recording, Western blot analysis (cyclic AMP response element-binding (CREB) proteins, phosphorylated CREB proteins, brain-derived neurotrophic factor, and parvalbumin) to examine the synaptic plasticity. The EPSP was remarkably increased in the AD-T group compared with in the AD-NT group. In the Western blot analysis, the differences among the groups were not significant. Hence, tACS can affect the long-lasting enhancement of synaptic transmission in mice models of AD.

Highlights

Alzheimer’s disease (AD) is a neurological disease characterized by progressive cognitive decline resulting in memory deficit and behavioral changes [1,2,3]
We confirmed the enhancement of synaptic plasticity in transgenic mice of AD via an electrophysiologic test through the stimulation of gamma Transcranial alternating current stimulation (tACS) in the frontal lobe
These findings support the results in previous human studies that tACS can improve cognitive function in patients with AD

Summary

Introduction

Alzheimer’s disease (AD) is a neurological disease characterized by progressive cognitive decline resulting in memory deficit and behavioral changes [1,2,3]. It is prevalent in a majority of dementia cases. Pharmacologic treatment is the main therapeutic modality for patients with AD; this therapeutic effect has been proven to be insufficient in ameliorating the state of patients affected by the disease. As an alternative to drug therapy, noninvasive brain stimulation (NIBS) has been studied in patients with AD. According to the studies published so far, cranial electrotherapy stimulation (CES), a type of NIBS, is known to be ineffective in improving cognitive function in the case of AD [14,15]

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