Regulation of Genes Related to Cognition after tDCS in an Intermittent Hypoxic Brain Injury Rat Model.

Background: Hypoxic brain injury is a condition caused by restricted oxygen supply to the brain. Several studies have reported cognitive decline, particularly in spatial memory, after exposure to intermittent hypoxia (IH). However, the effect and mechanism of action of IH exposure on cognition have not been evaluated by analyzing gene expression after transcranial direct current stimulation (tDCS). Hence, the purpose of this study was to investigate the effects of tDCS on gene regulation and cognition in a rat model of IH-induced brain injury. Methods: Twenty-four 10-week-old male Sprague−Dawley rats were divided into two groups: IH exposed rats with no stimulation and IH-exposed rats that received tDCS. All rats were exposed to a hypoxic chamber containing 10% oxygen for twelve hours a day for five days. The stimulation group received tDCS at an intensity of 200 µA over the frontal bregma areas for 30 min each day for a week. As a behavior test, the escape latency on the Morris water maze (MWM) test was measured to assess spatial memory before and after stimulation. After seven days of stimulation, gene microarray analysis was conducted with a KEGG mapper tool. Results: Although there were no significant differences between the groups before and after stimulation, there was a significant effect of time and a significant time × group interaction on escape latency. In the microarray analysis, significant fold changes in 12 genes related to neurogenesis were found in the stimulation group after tDCS (p < 0.05, fold change > 2 times, the average of the normalized read count (RC) > 6 times). The highly upregulated genes in the stimulation group after tDCS were SOS, Raf, PI3K, Rac1, IRAK, and Bax. The highly downregulated genes in the stimulation group after tDCS were CHK, Crk, Rap1, p38, Ras, and NF-kB. Conclusion: In this study, we confirmed that SOS, Raf, PI3K, Rac1, IRAK, and Bax were upregulated and that CHK, Crk, Rap1, p38, Ras, and NF-kB were downregulated in a rat model of IH-induced brain injury after application of tDCS.

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.