Comprehensive transcriptomic profiling of cortical and striatal regions in a postnatal mouse model of attention-deficit/hyperactivity disorder

Despite advances in understanding its genetic and neurobiological underpinnings, comprehensive molecular characterization, particularly at early developmental stages, remains underexplored. This study investigates transcriptomic alterations in the prefrontal cortex (PFC) and striatum (STR) of a postnatal ADHD mouse model induced by 6-hydroxydopamine (6-OHDA), which selectively eliminates dopaminergic neurons.

Employing bulk RNA sequencing (RNA-seq) coupled with weighted gene co-expression network analysis (WGCNA), we identified 369 DEGs in the PFC, 493 DEGs in the STR, and 32 modules in WGCNA, uncovering distinct expression profiles associated with ADHD. Functional enrichment analyses identified that PFC-DEGs were involved in PFC development, plasma membrane signaling, and transcriptional regulation. STR-DEGs were associated with STR development, locomotion, extracellular matrix, and response to amphetamine.