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.

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.

Acute myocardial infarction is the most common form of coronary artery disease, and myocardial ischemia–reperfusion injury remains a major challenge despite advances in reperfusion therapy. Endotoxin preconditioning has been linked to reduced ischemia–reperfusion injury, but mechanisms remain unclear, and prior studies have used varied assessment methods with inconsistent results. In this study, we confirmed the protective effect of endotoxin preconditioning and assessed its role in preserving mitochondrial respiration using a multi-model approach of in vivo ischemia–reperfusion rat model, ex vivo normothermic rat heart perfusion, and in vitro hypoxia–reoxygenation in neonatal rat cardiomyocytes. Hemodynamic and cell-based analyses were performed in control (n = 5), ischemia–reperfusion/hypoxia–reoxygenation (n = 4/3), and endotoxin-pretreated (n = 5/3) groups. Low-dose endotoxin pretreatment significantly preserved left ventricular function, myocardial oxygen consumption, and mitochondrial respiration (p < 0.001). Preservation of function was associated with reduced hypoxia-inducible factor 1-alpha (HIF-1α) expression and decreased mitochondrial superoxide production, indicating reduced oxidative stress. Nonlethal endotoxin pretreatment protects the myocardium from ischemia–reperfusion injury by sustaining mitochondrial respiration and limiting oxidative damage. These findings support further investigation in large animal models to better replicate human myocardial infarction and evaluate translational potential.