Therapeutic potential of prefrontal cortical stimulation for depression and dementia

Abstract

Introduction: Major depression and dementia pose major health challenges, worldwide. Despite enormous efforts have been made to search for a cure in depression and dementia, majority of these studies have failed. In this study, we investigated the potential roles of deep brain stimulation (DBS) for antidepressant and memory enhancement in animal models. Materials and Methods: The animals were stimulated in the medial prefrontal cortex (mPFC), and they were behaviourally tested for depressive-like and hippocampaldependent memory tests. For mechanisms, we investigated the hippocampal neuroplasticity and midbrain monoaminergic signalling using a combination of microarray, biochemical, immunohistochemical, and electrophysiological approaches. Results and Discussion: Our results demonstrated that DBS of the mPFC enhanced antidepressant-like activities and memory functions in rat models of stress-induced depression and aged-related cognitive impairment, respectively. Interestingly, we showed that mPFC DBS evoked the neurocircuitry pathway of depression that related to the midbrain monoaminergic system. We also revealed that mPFC DBS rescued the stress-induced dopaminergic neurodegeneration in the midbrain of animal model with vulnerability to stress-induced depression. For hippocampal-related mechanisms, there were significant increase of neurogenesis and dendritic arborisation in stimulated animals when compared to sham-control. Finally, our microarray study showed changes in distinct pattern of gene expression with G-protein-coupled receptor pathways, suggesting the roles of neuroplasticitydependent and -independent effects of DBS. Conclusion: Although we found significant antidepressant-like and memory enhancement by mPFC DBS, additional studies are needed to investigate the effects of DBS that look beyond neurogenesis and other pathways suggested by our findings.