Common prefrontal cortical gene expression profiles between adolescent SHR/NCrl and WKY/NCrl rats which showed inattention behavior

Abstract

Factor analyses of attention-deficit/hyperactivity (ADHD) symptoms divide the behavioral symptoms of ADHD into two separate domains, one reflecting inattention and the other, a combination of hyperactivity and impulsivity. Identifying domain-specific genetic risk variants may aid in the discovery of specific biological risk factors for ADHD. In contrast with data available on genes involved in hyperactivity and impulsivity, there is limited information on the genetic influences of inattention. Transcriptional profiling analysis in animal models of disorders may provide an important tool to identify genetic involvement in behavioral phenotypes. To explore some of the potential genetic underpinnings of ADHD inattention, we examined common differentially expressed genes (DEGs) in the prefrontal cortex of SHR/NCrl, the most validated animal model of ADHD and WKY/NCrl, animal model of ADHD-inattentive type. In contrast with Wistar rats, strain representing the "normal" heterogeneous population, SHR/NCrl and WKY/NCrl showed inattention behavior in the Y-maze task. The common DEGs in the PFC of SHR/NCrl and WKY/NCrl vs. Wistar rats are those involved in transcription (e.g. Creg1, Thrsp, Zeb2), synaptic transmission (e.g. Atp2b2, Syt12, Chrna5), neurological system process (e.g. Atg7, Cacnb4, Grin3a), and immune response (e.g. Atg7, Ip6k2, Mx2). qRT-PCR analyses validated expression patterns of genes representing the major functional gene families among the DEGs (Grin3a, Thrsp, Vof-16 and Zeb2). Although further studies are warranted, the present findings indicate novel genes associated with known functional pathways of relevance to ADHD which are assumed to play important roles in the etiology of ADHD-inattentive subtype.

Keywords: ADHD; Gene expression; Inattention; Prefrontal cortex; SHR/NCrl; WKY/NCrl.