INTEGRATED ANALYSIS OF MICROARRAY AND PROTEOMICS DATA BY HIPPOCAMPAL RAT NEURONS AND HUMAN IPS NEURONS TREATED WITH DIFFERENT DOSES OF LITHIUM

Background Lithium salts have a well-established role in the treatment of psychiatric disorders as major affective disorders and more recently Alzheimer disease. Experimental and clinical studies have provided evidence that lithium may exert neuroprotective effects at therapeutically and sub therapeutically doses. In animal model and cell culture models, lithium has been shown to increase neuronal viability through a combination of mechanisms that includes the inhibition of apoptosis, regulation of autophagy, increased mitochondrial function, and synthesis of neurotrophic factors. Objective: The Objective of the study is to compare biological process and pathways enriched in hippocampal neurons treated with different doses of lithium (0.02 mM, 0.2 mM and 2 mM) integrating genes and proteins differentially expressed. Methods Primary cultures of hippocampal neurons; Assessment of cell viability; Experimental design considerations, Microarray; LC-MS analyses; Data Analysis; Neural stem cell differentiation in Random differentiation; String Database and Functional enrichment analysis. Results The results showed that growing gene networks using differentially expressed genes and proteins as seeds alterations in mitochondria, ribosome and proteasome were observed in all lithium treatment doses. But also more specific biological process such as mitochondria respiratory chain, energy production (glucose and ATP) and apoptosis biological functions were enriched in each dose treatment. Discussion Given all the analyzes we can see that there is a dissociation dose effect of the treatment with lithium, the dose of 0.02Mm modified genes of degradation pathway proteins. The dose of 0.2Mm altered pathways of energy metabolism and the dose of 2Mm change related to nuclear and nuclear membrane. we can understand the specific function of each dose of the treatment.