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.

Redox and Immune Signaling in Schizophrenia: New Therapeutic Potential

“…We now turn our attention to the therapeutic potential of targeting brain redox and immune biology in SZ. Preclinical studies using animal models, as well as patient-derived blood and CSF studies, have identified some intriguing targets relevant to both processes ( Perkins et al, 2015 ; Kim et al, 2019 ; Nakao et al, 2021 ; Cuenod et al, 2022 ). These include the GSH/GPX/Gred and TRX/PRX/SRX systems, the NAD/NADH system, the MMP9/RAGE pathway, and bioenergetics-related micro-RNAs.…”

Calcium voltage-gated channel subunit alpha 1 C and glial fibrillary acidic protein signaling pathways as a selective biomarker in predicting the efficacy of liposomal loaded co-enzyme Q in the autistic rat model

“…Additionally, PPA oxidative stress causes membrane abnormalities in L -type calcium channels that directly affect the channel's shape or the number of channels, which results in an increase in calcium overload and brain malfunction. More evidence for the role of Calcium Channel Genes in ASD stems from the association of ASD with single-nucleotide polymorphism in the CACNA1C gene encoding a T-type Ca 2+ channel subunit [37] .…”

Downregulation of long non-coding RNAs in patients with bipolar disorder

“…The etiology of BD is still unknown, but family studies as well as adoption and twins studies suggest significant contribution of genetic factors 22 . In addition, evidence suggests that altered signaling pathways, including oxidative stress, is one of the general factors involved in the pathogenesis/neurobiology of BD 6 . Reactive oxygen species (ROS) are involved in induction of expression of the p53 tumor suppressor gene and cell aging.…”

“…One of the factors involved in activating these signaling pathways and apoptosis is oxidative stress 4 . Several studies have indicated that oxidative stress parameters including nitric oxide levels, antioxidant enzymes, and lipid peroxidation have been altered in patients with BD 5 , 6 . Rising evidence currently has shown long noncoding RNAs (lncRNAs) have a relevant function in the cellular response to DNA damage and oxidative stress 7 , 8 .…”