Transcranial Focal Stimulation modifies genetic expression in the cerebral cortex of naive rats

Transcranial Focal Stimulation (TFS) is an alternating-current Transcranial Electrical Stimulation technique with significant therapeutic potential. Nevertheless, the biological mechanisms responsible for the effects of TFS remain unknown. Using microarray technology, we evaluated the cerebral cortex transcriptome of rats receiving a short course (5 min) of TFS. After differential gene expression and enrichment analyses, we selected candidate genes of interest for further validation. Cerebral and hippocampal tissue of rats submitted to the same therapy were used for Western blot and immunohistochemistry to detect chosen proteins. Sham-stimulated rats were used as a reference. No differential gene expression was identified when analyzing hippocampal data. In the cerebral cortex samples, we found a total of 284 differentially expressed genes. We observed an increase in Sema4G proteins in the cerebral cortex and hippocampus (p < 0.001), and an increased expression of ZEB2 only in the hippocampus. Transcranial Focal Stimulation also increased c-Fos expression in the cerebral cortex, hippocampus, basolateral amygdala, and ventromedial hypothalamic nucleus (p < 0.001). Conclusion: A short course of TFS modifies the brain´s gene and protein expression profiles. The effects were more pronounced in the cerebral cortex than in the hippocampus. TFS also produces an increase in brain activity in cortical and subcortical regions. Additional research is necessary to validate our findings and evaluate the long-term effects of TFS.