Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
ADHD is a developmental disorder that manifests as a complex combination of genetic predisposition, neurotransmitter abnormalities, and environmental factors. The prevalence of ADHD in adults is estimated to be about 5%, and the number of patients receiving pharmacologic treatment is increasing. Methylphenidate (MPH) is used worldwide as a first-line treatment for ADHD. Recently, environmental factors such as smoking have been reported to alter the sperm epigenome and affect the phenotype in next generation. We have previously shown that paternal MPH exposure increases ADHD-like impulsivity in offspring of ICR mice, but the underlay mechanism is obscure. Therefore, we used inbred Balb/c mice to examine the effects of MPH on the sperm epigenome and on the behavior and gene expression in the next generation.
Sires (F0) were subcutaneously administered MPH for 28 days and mated with naive dams. Developmental assessments of offspring (F1) were performed at 4-21 days of age. Upon reaching 4.5 weeks of age, F1 were subjected to behavioral tests such as elevated plus-maze (EPM) test and RNA-seq of the brain were performed. Sperm were collected from F0 after mating for epigenomic analysis.
MPH administration to F0 had no significant effect on F1 development. However, EPM test showed that MPH administration to F0 caused F1 to acquire impulsivity. Paternal MPH exposure in male Balb/c mice heightened impulsivity in the F1, as similar to ICR mice. Results from the RNA-seq analysis of F1 brain and epigenome analysis of F0 sperm will be reported along with the findings mentioned above.
