Background: Alzheimer's disease (AD) is a degenerative brain disease that degrades memory and perception. Transcranial alternating current (tACS) is a non-invasive stimulation method used in rehabilitation medicine. Recently, tACS is used in various fields, and its effect has been reported to improve cognitive function. However, there are few studies about tACS applied to AD, and few papers based on animal experiments.
Objective: This study is to investigate the effect of tACS using the delta wavelength and square wave on the cognitive function of Alzheimer's disease in transgenic mouse.
Method: Twelve mice of 4 months old five familial AD (5XFAD) model were randomly divided into 4 groups; 5xFAD mouse stimulated with tACS (AD-treat group), 5xFAD mouse with no stimulation (AD-NT group), wild type mouse with stimulation (WT-treat group) and mouse with no stimulation (WT-NT group). Stimulation protocol was delivered at 2Hz, 1mA and square wave over F3 and F4 (bilateral front lobe) area for 20 minutes for 2 weeks (5 times a week). Y-maze performed for 7 minutes was applied to investigate spatial memory task. The hippocampus was extracted and confirmed through Western blot (BDNF, CREB and pCREB) and Excitatory Postsynaptic Potential (EPSP) was performed to confirm the synaptic plasticity of the hippocampus.
Result
The LTP result showed AD-treat group (137.03±6.25), AD-NT group (118.11±3.28), WT-treat group (147.36±4.18) and WT-NT group (173.33±8.47). EPSP significantly increased in AD-treat compared to that in the AD-NT (p<0.01). The AD-treat level of CREB and pCREB was higher than AD-NT, which was consistent with the result of Western blot. The spontaneous alternation test was AD-treat group (14.91±2.34), AD-NT group (11.36±5.47), WT-treat group (19.40±3.55) and WT-NT group (26.52±1.29).
Conclusion: In this study, we confirmed that stimulation of delta tACS of square wave in frontal lobe (F3 and F4) induced improvement of cognitive function in transgenic mouse. We demonstrated that the tACS induced LTP-like synaptic plasticity and memory enhancement in Alzheimer’s dementia thought the response via continuous production of pCREB, CREB and BDNF and presented a mechanism. |
