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

Genes (Basel). 2022 Oct 9;13(10):1824. doi: 10.3390/genes13101824.

Abstract

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.

Keywords: gene regulation; hypoxic brain injury; transcranial direct current stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Injuries*
  • Cognition
  • Hypoxia / genetics
  • Male
  • NF-kappa B
  • Oxygen
  • Phosphatidylinositol 3-Kinases
  • Rats
  • Rats, Sprague-Dawley
  • Transcranial Direct Current Stimulation*
  • bcl-2-Associated X Protein

Substances

  • bcl-2-Associated X Protein
  • NF-kappa B
  • Oxygen
  • Phosphatidylinositol 3-Kinases

Grants and funding

This research was funded by National Research Foundation of Korea (NRF-2019R1F1A1062089) and The APC was funded by a grant (BCRI-21032) from Chonnam National University Hospital Biomedical Research Institute.