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. 2022 Dec 23:16:1069484.
doi: 10.3389/fnins.2022.1069484. eCollection 2022.

Effects of transcranial direct current stimulation on brain cytokine levels in rats

Victoria T Ethridge  1   2   3 , Nathan M Gargas  1   2   3 , Martha J Sonner  1   3   4 , Raquel J Moore  5   6 , Shannon H Romer  1   2   3 , Candice Hatcher-Solis  6 , Joyce G Rohan  1
Affiliations

Effects of transcranial direct current stimulation on brain cytokine levels in rats

Victoria T Ethridge et al. Front Neurosci. .

Abstract

Transcranial direct current stimulation (tDCS) has shown therapeutic potential to mitigate symptoms of various neurological disorders. Studies from our group and others used rodent models to demonstrate that tDCS modulates synaptic plasticity. We previously showed that 30 min of 0.25 mA tDCS administered to rats induced significant enhancement in the synaptic plasticity of hippocampal neurons. It has also been shown that tDCS induces expression of proteins known to mediate synaptic plasticity. This increase in synaptic plasticity may underly the observed therapeutic benefits of tDCS. However, the anti-inflammatory benefits of tDCS have not been thoroughly elucidated. Here we report that three sessions of tDCS spaced 1-3 weeks apart can significantly reduce levels of several inflammatory cytokines in brains of healthy rats. Rats receiving tDCS experienced enhanced synaptic plasticity without detectable improvement in behavioral tests or significant changes in astrocyte activation. The tDCS-mediated reduction in inflammatory cytokine levels supports the potential use of tDCS as a countermeasure against inflammation and offers additional support for the hypothesis that cytokines contribute to the modulation of synaptic plasticity.

Keywords: cytokines; inflammation; plasticity; rats; tDCS.

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Conflict of interest statement

VE, NG, MS, and SR were employed by Leidos. VE, NG, and SR were employed by Odyssey Systems Consulting Group. MS was employed by ICON. RM was employed by Infoscitex. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Effects of transcranial direct current stimulation (tDCS) on hippocampal long-term potentiation (LTP). (A) Diagram showing the experimental timeline. Rats underwent surgery and 3 rounds of tDCS before LTP and cytokine levels were measured. (B) Normalized slope data showing tDCS effect on LTP. Administration of tDCS resulted in enhanced LTP in the Shaffer collateral-CA1 synapses of rat hippocampus. (C) Bar graph showing significant increase in LTP from rats given 3 rounds of tDCS (p = 0.009, n = 15 slices sham, n = 13 slices tDCS, Mann Whitney).
FIGURE 2
FIGURE 2
Effects of transcranial direct current stimulation (tDCS) on brain and plasma cytokine levels. (A) TNF-α was significantly reduced in the brains of rats stimulated with tDCS (*p = 0.03, n = 11, t-test). No significant difference was observed in plasma levels of TNF-α (p > 0.05). (B) IFN-γ was significantly reduced in the brains of rats stimulated with tDCS (*p = 0.004, n = 12, t-test). No significant difference was observed in plasma levels of IFN-γ (p > 0.05). (C) A non-significant decrease in IL-1β level was detected in brains of rats administered tDCS with p = 0.07 (n = 11 sham, 12 tDCS, t-test). Plasma levels of IL-1 β were below the detection limit. (D) A non-significant decrease in IL-5 was detected in brains of rats administered tDCS with p = 0.08 (n = 12, t-test). Plasma levels of IL-5 were below the detection limit. (E) IL-4 was significantly reduced in brains of rats stimulated with tDCS (*p = 0.04, n = 10 sham, 7 tDCS, t-test). No significant difference in plasma level of IL-4 (p > 0.05). (F) IL-10 was significantly reduced in brains of rats administered tDCS (*p = 0.005, n = 9 sham, 12 tDCS, t-test). Plasma level of IL-10 was not significantly different (p > 0.05). (G) IL-13 was significantly reduced in brains of rats stimulated with tDCS (*p = 0.01, n = 12 sham, 11 tDCS, t-test). There was no significant difference in IL-13 in the plasma (p > 0.05).
FIGURE 3
FIGURE 3
Effects of transcranial direct current stimulation (tDCS) on astrocyte activation. Micrograph images from small confocal stacks (z = 9 × 1 μm steps) with astrocytes revealed with GFAP immunoreactivity (Red) and neurons revealed with green fluorescent Nissl staining. (A) Image of hippocampus slice from a control (sham) rat. (B) Image of hippocampus slice from a rat administered one round of tDCS. Scale bar = 400 μm (C) Enlarged image from a control (sham) rat showing astrocytes. Area enlarged is indicated as the white box in A. (D) Enlarged image from a rat administered one round of tDCS showing astrocytes. Area enlarged is indicated as the white box in B. (E) Bar graph showing no significant effect of tDCS on integrated optical density (p = 0.985, n = 3 rats, t-test) (F) Bar graph showing a minor decrease in astrocyte nuclei per mm2, effect was not statistically significant (p = 0.211, n = 3 rats, 3 slices per rat, t-test).
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