Electrical stimulation enhances mood and memory functions in animal models

Abstract

Memory dysfunction is the main symptom of dementia-related disorders. In this study, we tested the hypotheses that electrical stimulation of the medial prefrontal cortex (mPFC) enhanced memory- and mood-related behaviors in animal models. Our data demonstrated that stimulation of the mPFC evoked antidepressant effects. Further, we have shown that mPFC stimulation enhanced neurogenesis in the hippocampus, mitigating the deleterious effects of memory dysfunction conditions and improved the learning and memory functions in the Morris water maze and object recognition tests. Our results showed a remarkable increase of neural progenitors, surviving BrdU-positive cells, and dendritic arborization after chronic mPFC stimulation as compared to the sham. To support these findings, immunofluorescence studies revealed co-localization of c-Fos immediate-early gene activation with the doublecortin and the BrdU-labeled cells in the hippocampal dentate gyrus, indicating their pivotal roles on memory functions. These effects were further supported by the hippocampi upregulated neuroplasticity-related gene expression involving proliferation, differentiation, and migration using microarrays and quantitative real-time PCR techniques. Besides, we have also found that mPFC stimulation evoked a specific neurocircuitry modulation of the serotonergic pathways, linking the dorsal raphe nucleus in regulation of mood-related and hippocampal-dependent memory behaviors. Overall, our findings suggested that mPFC stimulation has the potential to be developed into a therapy to treat patients suffering from dementia as well as treatment-resistant depression. Importantly, its mechanisms by which stimulation improves mood and memory functions are likely to be mediated by hippocampal neuroplasticity and serotonergic neurotransmission.