Introduction: Low lithium concentration has a significant positive effect in synaptic plasticity and reduces cell toxicity. Lithium negatively regulates the expression and activity of glycogen synthase kinase 3b (GSK3b). GSK3b have different partners based on protein-protein interaction databases, here on called as the “GSKoma”. The aim of the study is to evaluate the enrichment of the GSKoma in differentially expressed genes related to neuroprotection in hippocampal neurons with different doses of lithium. Methods: Primary cultures of hippocampal neurons were treated for 7 days with lithium (0.02mM,0.2mMand2mM). The Agilent860k microarray platform were used. The samples were analyzed in the MeV, with a delta of 1.4 and FDR of 5% and R v3.4. GSKoma was constructed using PathCard and String program. Results: Up regulated genes were identified: 8 (0.02mM), 126 (0.2mM) and 739 (2mM). Dow-regulated genes were identified: 36 (0.02mM), 1132 (0.2mM) and 1603 (2mM). GSKoma was made up of 182 proteins that directly interact with GSK3b. The results showed that probably GSK3b is not the main route of different doses of lithium on gene expression, since there was no significant enrichment of the GSKoma using MSET. Analyzes of biological processes showed that the 0.02mM dose was related to: cortex tangential migration; forebrain degeneration of neurons and forebrain differentiation; the dose of 0.2mM ion transport, metal ions transport, ion transmembrane transport; 2mM response to stimulus and response to organic substance. Whereas the biological processes related to GSK3b block were: response to organic substance; response to oxygen containing compound; response to endogenous stimulus and response to organic cyclic compound. Conclusion: GSK3b pathway did not appear as the main event for the response to treatment with lithium in therapeutic and subtherapeutic doses.

Effect of lithium at therapeutic and subtherapeutic doses in GSK3beta autonomous pathways at primary hippocampal neurons cell culture

2019 Spring National Meeting

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