Kim Wang-In, Han Jae-Young, Song Min-Keun, Park Hyeng-Kyu, Jo Jihoon
Department of Physical & Rehabilitation Medicine, Regional Cardiocerebrovascular Center, Center for Aging and Geriatrics, Chonnam National University Medical School & Hospital, Gwangju 61469, Korea.
NeuroMedical Convergence Lab, Biomedical Research Institute, Chonnam National University Hospital, Jebong-ro, Gwangju 61469, Korea.
Brain Sci. 2020 Aug 12;10(8):547. doi: 10.3390/brainsci10080547.
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.
阳极经颅直流电刺激（tDCS）是一种无痛的非侵入性方法，据报道可通过刺激大脑改善阿尔茨海默病（AD）的认知功能。然而，其潜在机制仍不清楚。因此，本研究使用电生理和病理方法研究了5xFAD AD小鼠模型中的认知效应。我们使用了雄性5xFAD C57BL/6J小鼠和雄性C57BL/6J野生型小鼠；通过DNA测序确认了痴呆模型。经验证的AD小鼠和野生型小鼠被随机分为四组，每组五只：接受tDCS治疗的诱导AD组（Stim-AD）、未接受tDCS的诱导AD组（noStim-AD）、接受tDCS的非诱导组（Stim-WT）和未接受tDCS的非诱导组（noStim-WT）。在刺激组中，小鼠在额前囟区域接受强度为200μA的tDCS刺激20分钟。治疗2周后，我们将小鼠断头，从大脑中取出海马体，通过兴奋性突触后电位（EPSP）记录确认其神经元激活，并使用蛋白质免疫印迹法对剩余组织进行分子实验。与noStim-AD组相比，Stim-AD组的EPSP显著增加，与非诱导组Stim-WT和noStim-WT相当。与noStim-AD组相比，Stim-AD组中环状单磷酸腺苷反应元件结合蛋白（CREB）、磷酸化CREB（pCREB）和脑源性神经营养因子（BDNF）水平无显著差异。本研究表明，转基因5xFAD小鼠模型双侧额叶的tDCS影响长时程增强，提示可能增强认知功能。
