The effect of chronic lithium treatment on hippocampal progenitor cells: Transcriptomic analysis and systems pharmacology

ObjectiveTo identify the genomics underpinning the increased volume of the hippocampus after long-term administration of lithium (Li) in bipolar disorder patients, hypothesizing the possible contribution of cell growth and differentiation pathways to this complication. MethodsRNA-seq profiles of four samples of hippocampal progenitor cells chronically treated with a high dose of Li and three samples chronically treated with the therapeutic dose were retrieved from NCBI-GEO. The raw data underwent filtration, quality control, expression fold change, adjusted significance, functional enrichment, and pharmacogenomic analyses. ResultsCCND1, LOXL2, and PRNP were identified as the genes involved in the drug response and the chronic effects of Li in the hippocampal cells. GSK-3 & beta; was also a hub in the pharmacogenomic network of Li. In addition, ZMPSTE24 and DHX35 were identified as the important genes in lithium therapy. ConclusionsAs shown by gene ontology results, these findings conclude that lithium may increase the size of the hippocampus in bipolar patients by stimulating the generation of new neurons and promoting their differentiation into neuroblasts, neurons, or microglia.

Automated summary

This study aimed to investigate the genomics underlying the enlarged volume of the hippocampus in bipolar disorder patients after long-term lithium administration. The results suggest that lithium may promote the generation of new neurons and their differentiation into neuroblasts, neurons, or microglia, leading to hippocampal enlargement. Several genes, including CCND1, LOXL2, and PRNP, were identified as being involved in the drug response and chronic effects of lithium in hippocampal cells. GSK-3β was also found to be a key hub in the pharmacogenomic network of lithium.