Exploring PDE5A upregulation in bipolar disorder: insights from single-nuclei RNA sequencing of human basal ganglia

The basal ganglia has been considered as a potential target implicated in bipolar disorder (BD), but there is currently limited research on molecular changes. In this study, we conducted single-nucleus RNA sequencing on 30,752 nuclei from the putamen, caudate nucleus, pallidum, and substantia nigra of postmortem brains without apparent neurological and psychiatric disorders, as well as 24,672 nuclei from the same brain regions of BD patients. By performing differential expression analysis, weighted gene co-expression network analysis (WGCNA), single-cell regulome analysis (SCENIC), and CellChat analysis, we investigated the cell type-specific gene expression and network changes in the basal ganglia of BD patients compared to healthy individuals. These findings provide an important direction for the study of bipolar disorder. Overall design: To investigate the specific molecular changes in the striatum of mice after PDE5A overexpressing, we used three control groups and OE groups for RNA-seq analysis.