Effect of organic lithium salts on the levels Akt/mTOR-signaling pathway proteins in peripheral blood mononuclear cells of patients with bipolar disorder

Introduction. Nowadays, the development and study of new lithium compounds with combined cytoprotective and mood-stabilizing activity is in the process. In that way organic lithium salts based on acids which are metabolites of cellular energy exchange are promising. The Akt/mTOR-signaling pathway is an important link in the regulation of cellular functions, and therefore the study of the effect of newly synthesized organic lithium salts on its activity is relevant for the understanding of their action mechanism. Objective. The effect of lithium carbonate, fumarate, py-ruvate and succinate on the content of total and phosphorylated forms of 11 proteins of the Akt/mTOR-signaling pathway in peripheral blood mononuclear cells of patients with bipolar disorder (BD) was studied. Material and Methods. Whole venous blood for subsequent isolation of cells was taken from 12 patients with BD, 7 women and 5 men. Median age was 48.0 years (37.5-52.0). The obtained mononuclear cells were incubated for 24 hours with car-bonate, fumarate, pyruvate or lithium succinate at a concentration of 1,2 mmol/l. Assessment of total and phospho-forms of 11 proteins of the Akt/mTOR-signaling pathway in cell lysates was made using «Luminex xMAP» the mul-tiplex technology on the «MAGPIX» multiplex analyzer (Merk, Germany). Statistical analysis was carried out using SPSS software (version 20.0). The median, first and third quartiles were calculated and the Mann-Whitney test was used to compare quantitative variables. Results. It was shown that lithium pyruvate significantly heightened the intra-cellular level of total forms of proteins GSK-3α and β, Akt, mTOR, PTEN, IRS1, P70S6K, TSC2, as well as phos-pho-form of P70S6K. Under the action of lithium pyruvate significant decrease in the phospho-forms of GSK-3β, Akt and mTOR was revealed. Conclusion. Thus, the data obtained indicated the effect of lithium pyruvate on the activity of the Akt/mTOR-signaling pathway in mononuclear cells of patients with BD, which may be one of the possible mechanisms of the its cytoprotective action, which we revealed earlier. The results could serve as a basis for further search and study of new lithium compounds with combined cytoprotective and/or mood-stabilizing activity