Vipr2 Gene Expression Is Upregulated in the Nucleus Accumbens of Spontaneous Hypertensive Rats During Early Life

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders. Recent methylome analyses have shown that peripheral DNA methylation levels in the VIPR2 gene, which encodes vasoactive intestinal peptide receptor 2, are correlated with ADHD symptoms. However, mRNA expression and DNA methylation levels of the VIPR2 gene in the brain in ADHD are unknown. In this study, we examined the mRNA expression and DNA methylation levels of the Vipr2 gene in the brains of spontaneous hypertensive rats (SHRs), which are used as an animal model of ADHD.

The mRNA levels of Vipr2 and related genes were analyzed in the prefrontal cortex, nucleus accumbens (NAc), amygdala, and hippocampus of SHRs and Wistar Kyoto rats (WKYs), a reference strain, by quantitative reverse transcription polymerase chain reaction. DNA methylation levels at the cytosine-phosphate-guanine (CpG) islands of the Vipr2 gene were evaluated in the NAc of WKYs and SHRs by bisulfite sequencing.

The mRNA level of Vipr2 was significantly higher in the NAc, but not in the prefrontal cortex, amygdala, or hippocampus, of male SHRs compared with male WKYs at 4 weeks old. Upregulation of the mRNA level of Vipr2 was observed before 4 weeks old and in females. In contrast, there were no differences in DNA methylation levels at the CpG islands of the Vipr2 gene in the NAc between WKYs and SHRs.

DNA methylation was not correlated with upregulation of Vipr2 mRNA in SHRs. Further studies are needed to clarify the involvement of Vipr2 mRNA upregulation in ADHD-like symptoms.