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

Author:

Jahandideh Mina1,Ebrahimi Erfan2,Farzaei Mohammad Hosein3,Barzegari Ebrahim1ORCID

Affiliation:

1. Medical Biology Research Center Health Technology Institute Kermanshah University of Medical Sciences Kermanshah Iran

2. Student Research Committee Kermanshah University of Medical Sciences Kermanshah Iran

3. Pharmaceutical Sciences Research Center, Health Institute Kermanshah University of Medical Sciences Kermanshah Iran

Abstract

AbstractObjectiveTo 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‐3β 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.

Funder

Kermanshah University of Medical Sciences

Publisher

Wiley

Subject

Behavioral Neuroscience

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