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

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.

Cognitive Function Improvement in Mouse Model of Alzheimer's Disease Following Transcranial Direct Current Stimulation.

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.

Regulation of gene expression after combined scalp acupuncture and transcranial magnetic stimulation in middle cerebral artery occlusion mice.

BACKGROUND: The effect of combined repetitive transcranial magnetic stimulation (rTMS) and scalp acupuncture stimulation (SAS) on middle cerebral artery occlusion (MCAO) mice has not yet been reported. The regulation of gene expression after combined stimulation remains unclear. OBJECTIVE: To analyze gene expression patterns through ribonucleic acid (RNA) sequencing. METHODS: Thirty-six 8-weeks-old C57BL/6J male mice weighing 50-60 grams were used for this experiment. The MCAO was induced with 60-min occlusion and subsequent reperfusion of the middle cerebral artery. Experimental mice were randomly assigned to four groups, with nine mice in each group, as follows: control group (no treatment), SAS group (10 minutes SAS), rTMS group (1 Hz rTMS), and combined group (1 Hz rTMS and SAS). Stimulation was performed from the 3rd day to the 7th day after the induction of MCAO. All mice were sacrificed, and brain tissues were taken from the motor area of the MCAO lesion. We analyzed their gene expression profiles using RNA sequencing technology. RESULTS: After stimulation, the grip strength increased in the SAS and rTMS group compared to the control and combined group. The nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) was the key up-regulated protein in the SAS group while src homologus and collagene gene (SHC) and p90 ribosomal protein S6 kinases (p90RSK) were key up-regulated proteins in the rTMS group. However, the C-terminal src kinase-homologous kinase (CHK) was down-regulated whereas p90RSK was up-regulated in the combined group based on the RNA sequencing analysis. CONCLUSIONS: Each stimulation method showed different patterns with neurotrophin signaling pathway including NFκB, SHC, p90RSK, and CHK. These can be used in further mechanistic studies about gene expression related to neurorecovery.

Evaluation of Anti-Inflammatory Potential of the New Ganghwaljetongyeum on Adjuvant-Induced Inflammatory Arthritis in Rats.

Ganghwaljetongyeum (GHJTY) has been used as a standard treatment for arthritis for approximately 15 years at the Korean Medicine Hospital of Dongshin University. GHJTY is composed of 18 medicinal herbs, of which five primary herbs were selected and named new Ganghwaljetongyeum (N-GHJTY). The purpose of the present study was to observe the effect of N-GHJTY on arthritis and to determine its mechanism of action. After confirming arthritis induction using complete Freund's adjuvant (CFA) in rats, N-GHJTY (62.5, 125, and 250 mg/kg/day) was administered once a day for 10 days. In order to determine pathological changes, edema of the paws and weight were measured before and for 10 days after N-GHJTY administration. Cytokine (TNF-α, IL-1ß, and IL-6) levels and histopathological lesions in the knee joint were also examined. Edema in the paw and knee joint of N-GHJTY-treated rats was significantly decreased at 6, 8, and 10 days after administration, compared to that in the CFA-control group, while weight consistently increased. Rats in N-GHJTY-treated groups also recovered from the CFA-induced pathological changes and showed a significant decline in cytokine levels. Taken together, our results showed that N-GHJTY administration was effective in inhibiting CFA-induced arthritis via anti-inflammatory effects while promoting cartilage recovery by controlling cytokine levels.