Differentially Expressed Genes Related with Hyperactivity and Associated Behavioral Disorders

Extremely high levels of physical activity (hyperactivity) share physiological characteristics with behavioral disorders such as Bipolar Disorder and Attention Deficit Hyperactivity Disorder. The striatum coordinates multiple aspects of behavior and striatum gene expression patterns have been associated with neuropsychiatric disorders. A mouse line selected for increased home cage activity (High-Active line) is an effective model to understand genetic factors involved in neurobiological processes influencing behavioral disorders. The objective of this study was to understand the differences in the striatum transcriptome between a High-Active and a Control mouse line. The bioinformatics analysis of RNA-Seq measurements included FastQC to evaluate the quality of reads, and Tuxedo pipeline for alignment and differential expression analysis. Approximately 680 genes were differentially expressed (FDR-adjusted P-value < 0.05) between the lines. Among these genes, Early Growth Response 2 (EGR2), Solute Carrier Family 6 Member 19 (SLC6A19), and Calcium Channel, Voltage-Dependent, Alpha 2/Delta Subunit 2 (CACNA2D2) were over-expressed in High-Active line relative to Control mice. EGR2 is associated with Bipolar Disorder, behavior, learning, and memory, while SLC6A19 pertains to the same family as SLC6A3, which is related with susceptibility of Attention Deficit Hyperactivity Disorder. Also, genes in the calcium channel family such as CACNA2D2 have been associated with neuropsychiatric disorders. Hypergeometric analyses of the differentially expressed genes using DAVID identified enriched (FDR-adjusted P-value < 0.05) Gene Ontology terms related with neuron differentiation and neuron development. These results offer insights into the genes and pathways associated with hyperactivity that could also be dysregulated in associated behavioral disorders.