Gsk3 Signalling and Redox Status in Bipolar Disorder: Evidence from Lithium Efficacy

Abstract

Objective. To discuss the link between glycogen synthase kinase-3 (GSK3) and the main biological alterations demonstrated in bipolar disorder (BD), with special attention to the redox status and the evidence supporting the efficacy of lithium (a GSK3 inhibitor) in the treatment of BD. Methods. A literature research on the discussed topics, using Pubmed and Google Scholar, has been conducted. Moreover, a manual selection of interesting references from the identified articles has been performed. Results. The main biological alterations of BD, pertaining to inflammation, oxidative stress, membrane ion channels, and circadian system, seem to be intertwined. The dysfunction of the GSK3 signalling pathway is involved in all the aforementioned “biological causes” of BD. In a complex scenario, it can be seen as the common denominator linking them all. Lithium inhibition of GSK3 could, at least in part, explain its positive effect on these biological dysfunctions and its superiority in terms of clinical efficacy. Conclusions. Deepening the knowledge on the molecular bases of BD is fundamental to identifying the biochemical pathways that must be targeted in order to provide patients with increasingly effective therapeutic tools against an invalidating disorder such as BD.

Xanthine-Catechin Mixture Enhances Lithium-Induced Anti-Inflammatory Response in Activated Macrophages In Vitro

“…After each treatment, total RNA was extracted using Trizol reagent (Invitrogen Life Technologies, Carlsbad, California, USA). Expression of most genes was quantified, as described previously by Luca et al [ 3 ]. For performing reverse transcription, RNA was added to the samples (1 μ L) with 0.2 μ L DNase (Invitrogen Life Technologies) for 5 min at 37°C and the samples were heated at 65°C for 10 min.…”

“…Pharmacologically, Li exerts different effects, including anti-inflammatory effects, on various biological and biochemical pathways, unlike conventional drugs that interact with specific molecular targets. Li inhibits the expression of glycogen synthase kinase 3 (GSK3), a proinflammatory enzyme that is directly implicated in the pathogenesis of mood disorders such as BD (Luca et al [ 3 ]).…”

Oxidative Stress-Related Endothelial Damage in Vascular Depression and Vascular Cognitive Impairment: Beneficial Effects of Aerobic Physical Exercise

“…The consequent ROS overproduction in the vascular system, including brain circulation, could be partially related to the overexpression of NADPH oxidases, characterizing the elderly [61]. In addition, OS determines the hyperactivation of glycogen synthase kinase (GSK-3) and, consequently, an alteration of mitochondrial permeability, recognized to exert a pivotal role in the pathogenesis of atherosclerosis [62,63]. Moreover, aging is characterized by microglial hyperactivation.…”

Lityuma Tedavi Yanıtının Klinik, Biyolojik ve Genetik Yordayıcıları

“…GSK-3β inactivates glycogen synthase and plays a role in many metabolic pathways such as protein synthesis and plasticity in the brain. Phosphorylated GSK-3β has been reported to play an important role in the regulation of oxidative stress, neuroinflammation, and neurogenesis pathways and in the pathogenesis of BD (Gould et al 2004, Can et al 2014, Luca et al 2016. Studies investigating the relationship between GSK-3β polymorphisms and lithium treatment response have found that there is an association between rs2199503 and rs6438552 polymorphisms and lithium treatment response (Can et al 2014).…”