Abstract

Anodal transcranial direct current stimulation (tDCS) is a painless noninvasive method that reportedly improves cognitive function in Alzheimer’s disease (AD) by stimulating the brain. However, its underlying mechanism remains unclear. Thus, the present study investigates the cognitive effects in a 5xFAD AD mouse model using electrophysiological and pathological methods. We used male 5xFAD C57BL/6J and male C57BL/6J wild-type mice; the dementia model was confirmed through DNA sequencing. The verified AD and wild-type mice were randomly assigned into four groups of five mice each: an induced AD group receiving tDCS treatment (Stim-AD), an induced AD group not receiving tDCS (noStim-AD), a non-induction group receiving tDCS (Stim-WT), and a non-induction group not receiving tDCS (noStim-WT). In the Stim group, mice received tDCS in the frontal bregma areas at an intensity of 200 µA for 20 min. After 2 weeks of treatment, we decapitated the mice, removed the hippocampus from the brain, confirmed its neuronal activation through excitatory postsynaptic potential (EPSP) recording, and performed molecular experiments on the remaining tissue using western blots. EPSP significantly increased in the Stim-AD group compared to that in the noStim-AD, which was comparable to that in the non-induced groups, Stim-WT and noStim-WT. There were no significant differences in cyclic amp-response element binding protein (CREB), phosphorylated CREB (pCREB), and Brain-derived neurotrophic factor (BDNF) levels in the Stim-AD group compared to those in the noStim-AD group. This study demonstrated that a tDCS in both frontal lobes of a transgenic 5xFAD mouse model affects long-term potentiation, indicating possible enhancement of cognitive function.

Highlights

  • Alzheimer’s disease (AD), with anterograde amnesia as its key symptom, is a neurodegenerative disorder characterized by brain dysfunction including the loss of cognitive function and behavior.AD dementia is prevalent in the elderly population and deteriorates the quality of lifeBrain Sci. 2020, 10, 547; doi:10.3390/brainsci10080547 www.mdpi.com/journal/brainsciBrain Sci. 2020, 10, 547 in the aging population [1]

  • We aimed to identify the effects of Transcranial direct current stimulation (tDCS) on cognitive function improvement and the underlying mechanism using the genetic dementia model 5xFAD

  • There were no significant differences in cyclic amp-response element binding protein (CREB), phosphorylated CREB (pCREB), or Brain-derived neurotrophic factor (BDNF) protein expression in the Stim-AD group relative to the noStim-AD group. (Figure 2)

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Summary

Introduction

Brain Sci. 2020, 10, 547; doi:10.3390/brainsci10080547 www.mdpi.com/journal/brainsci. Brain Sci. 2020, 10, 547 in the aging population [1]. Medical treatments for dementia include cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists [2]. These drugs are ineffective in some patients, are expensive, and are prone to side effects after long-term use. Since direct stimulation is clinically ineffective, the indirect method of noninvasive transcranial magnetic/electrical stimulation is being actively researched. This stimulation method has been applied in various fields and proven effective according to clinical and animal research. Transcranial direct current stimulation (tDCS) is a brain stimulation technique used to neuromodulate a brain area through small electrodes that emit a weak direct current on the skull [5]

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