The Role Of Mitofusin-2 And Mitochondrial Dysfunction In The Nucleus Accumbens During Depression And Anxiety

Abstract

Depression is a mood disorder characterized by symptoms that include anhedonia, a lack of energy, dysregulation of sleep, and thoughts of suicide. Depression is often comorbid with anxiety disorders, which are mood disorders characterized by increased arousal and other specific behavioral patterns such as restlessness and difficulty concentrating that can interfere with daily activities. These disorders are of considerable interest to current neurological research, especially to find new means of efficacious treatment due to the delayed onset of efficacy and inadequate response/remission rate of typical antidepressants. Selective serotonin reuptake inhibitors (SSRIs) are the primary class of antidepressants currently in use, developed alongside the monoamine theory of depression. However, the introduction of new hypotheses, like the neuroplasticity hypothesis of depression recontextualizes the understanding of current antidepressants, leaving room for the development of new therapeutic methods. Specifically, the nucleus accumbens (NAc) has been of considerable interest to research surrounding these mood disorders due to its projections to and from various regions of the forebrain that have been associated with the comorbid behaviors found in anxiety and depression. The NAc is largely composed of medium spiny neurons (MSNs), which are divided based on the specific expression of dopamine receptors. MSNs specifically express dopamine type 1 (D-1) or dopamine type 2 (D-2) receptors. Within these neurons, mitochondrial proteins have been shown to influence depressive and anxiety-like behavior, introducing them as a novel target for future therapeutic efforts.