Abstract
Major depression is a highly prevalent disorder, and its symptoms include a depressed mood, loss of interest or pleasure, suicidal thoughts, reduced motivation, and hopelessness. While the etiology of this disorder is multifactorial and poorly understood, increasing evidence suggests that impaired neuronal plasticity contributes to one of the key underlying mechanisms. Neuronal plasticity includes sustained modifications in synaptic structure and function that require de novo gene expression. The regulation of gene expression is a critical molecular mechanism mediating stable adaptations and maladaptations in the brain. Indeed, disruptions in transcription occur in various brain areas in preclinical models of depression and in patients with depression. Recent studies have suggested that histone deacetylases SIRTs-mediated gene transcription and/or SIRT1-dependent regulation of cellular homeostasis have important roles in the pathophysiology and the treatment of depression. Genetic studies suggest that the SIRT1 gene is associated with mood and anxiety disorders. Animal studies also suggest important roles of SIRTs in neuroplasticity, depression-like behavior, and stress responses. Here, we review new information regarding current understanding of SIRTs-mediated pathways that may impact depression. These novel mechanisms of action may lead to new therapeutic strategies for treating major depression.
