Abstract
Despite its extensive use in clinical studies, the molecular mechanisms underlying the effects of transcranial direct current stimulation (tDCS) remain to be elucidated. We previously described subacute effects of tDCS on immune- and stem cells in the rat brain. To investigate the more immediate effects of tDCS regulating those cellular responses, we treated rats with a single session of either anodal or cathodal tDCS, and analyzed the gene expression by microarray; sham-stimulated rats served as control. Anodal tDCS increased expression of several genes coding for the major histocompatibility complex I (MHC I), while cathodal tDCS increased the expression of the immunoregulatory protein osteopontin (OPN). We confirmed the effects of gene upregulation by immunohistochemistry at the protein level. Thus, our data show a novel mechanism for the actions of tDCS on immune- and inflammatory processes, providing a target for future therapeutic studies.
Highlights
Transcranial direct current stimulation has been applied in experimental and clinical settings for more than 20 years and may facilitate rehabilitation after stroke as suggested by clinical data (Hummel et al, 2005; Sparing et al, 2009)
Of all the other groups, comparing ipsilaterally stimulated to contralaterally stimulated hemispheres, or contralaterally stimulated hemispheres to sham stimulation, only cathodal ipsilateral transcranial direct current stimulation (tDCS) compared to cathodal contralateral stimulation resulted in a significant difference of one gene that was downregulated (Supplementary Table S1C)
TDCS effects will reflect in the unstimulated hemisphere, albeit to a lower extent, which explains the lack of significant changes between the unstimulated hemisphere and sham
Summary
Transcranial direct current stimulation (tDCS) has been applied in experimental and clinical settings for more than 20 years and may facilitate rehabilitation after stroke as suggested by clinical data (Hummel et al, 2005; Sparing et al, 2009). TDCS evokes various cellular effects on neural stem cells, neurons, astrocytes, oligodendrocytes, and microglia exceeding its primary neurophysiological actions: In the healthy rat brain, tDCS increases proliferation and migration of endogenous neural stem cells and activates microglia as the brain-resident immune cells (Rueger et al, 2012a; Keuters et al, 2015) Both anodal and cathodal tDCS induce neurogenesis, both in healthy animals (Braun et al, 2016) as well as after experimental stroke (Braun et al, 2016; Pikhovych et al, 2016). Expression changes on the transcriptome can be expected after a few hours after a stimulus, we chose to investigate the acute tDCS-induced transcriptome in an unbiased microarray approach 6 h after tDCS
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