Role of Oxidative Stress and Ca2+ Signaling in Psychiatric Disorders

Abstract

Psychiatric disorders are caused by complex and diverse factors, and numerous mechanisms have been proposed for the pathogenesis of these disorders. Accumulating evidence suggests that oxidative stress is one of the general factors involved in the pathogenesis/pathophysiology of major psychiatric disorders, including bipolar disorder, depression, anxiety disorder, and schizophrenia. Indeed, some clinical trials have shown improvement of the symptoms of these disorders by antioxidant supplementation. However, the molecular basis for the relationship between oxidative stress and the pathogenesis of psychiatric disorders remains largely unknown. In general, Ca²⁺ channels play central roles in neuronal functions, including neuronal excitability, neurotransmitter release, synaptic plasticity, and gene regulation, and genes that encode Ca²⁺ channels have been found to be associated with psychiatric disorders. Notably, a class of Ca²⁺-permeable transient receptor potential (TRP) cation channels is activated by changes in cellular redox status, whereby these TRP channels can link oxidative stress to Ca²⁺ signals. Given the unique characteristic of redox-sensitive TRP channels, these channels could be a target for delineating the pathogenesis or pathophysiology of psychiatric disorders. In this review, we summarize the outcomes of clinical trials for antioxidant treatment in patients with psychiatric disorders and the current insights into the physiological/pathological significance of redox-sensitive TRP channels in the light of neural functions, including behavioral phenotypes, and discuss the potential role of TRP channels in the pathogenesis of psychiatric disorders. Investigation of redox-sensitive TRP channels may lead to the development of novel therapeutic strategies for the treatment of psychiatric disorders.

Keywords: Ca2+ signaling; TRP channels; behavior; oxidative stress; psychiatric disorders.