Hippocampal transcriptome Analysis in Clock-delta19 mice identifies pathways associated with glial cell differentiation and myelination

Background: Clock-delta19 mice demonstrate behavioral characteristics and neurobiological changes that closely resemble those observed in bipolar disorder (BD), including manic-like behavior, emotional variability, disrupted rhythms, and responses to medication. Notably, abnormalities in the hippocampus have been observed in patients with BD, yet direct molecular investigation of human hippocampal tissue remains challenging due to its limited accessibility.Methods: To model BD, Clock-delta19 mice were employed. Weighted gene co-expression network analysis (WGCNA) was utilized to identify mutation-related modules, and changes in cell type proportions were determined using the computational deconvolution CIBERSORTx. Furthermore, GeneMANIA and protein-protein interactions (PPIs) were leveraged to construct a comprehensive interaction network.Results: 174 differentially expressed genes (DEGs) were identified, revealing abnormalities in biological pathways related to rhythmic processes, and various cell functions including morphology, differentiation, and receptor activity. Analysis identified 5 modules strongly correlated with the mutation, with functional enrichment highlighting disturbances in rhythmic processes and neural cell differentiation due to the mutation. Furthermore, alterations in cell populations were observed, with a decrease in neural stem cells (NSC), and an increase in astrocyte-restricted precursors (ARP), ependymocytes (EPC), and hemoglobin-expressing vascular cells (Hb-VC) in the mutant mice. A network comprising 12 genes that link rhythmic processes to neural cell differentiation in the hippocampus was also identified.