Genome-Wide DNA Methylation Profiling Reveals Epigenetic Changes in the Rat Nucleus Accumbens Associated With Cross-Generational Effects of Adolescent THC Exposure

• DOI: 10.1038/npp.2015.155
• Publication Date: 2015-06-05T11:03:14Z
• Authors: Corey T Watson; Henrietta Szutorisz; Paras Garg; Qammarah Martin; Joseph A Landry; Andrew J Sharp; Yasmin L Hurd
• Keywords: Male; 0301 basic medicine; Psychotropic Drugs; Reverse Transcriptase Polymerase Chain Reaction; DNA Methylation; Nucleus Accumbens; Epigenesis, Genetic; 3. Good health; 03 medical and health sciences; Maternal Exposure; Paternal Exposure; Animals; Original Article; Female; Rats, Long-Evans; Dronabinol; RNA, Messenger; Promoter Regions, Genetic

Drug exposure during critical periods of development is known to have lasting effects, increasing one's risk for developing mental health disorders. Emerging evidence has also indicated the possibility drug even impact subsequent generations. Our previous work demonstrated that adolescent Δ9-tetrahydrocannabinol (THC), main psychoactive component marijuana (Cannabis sativa), in a Long-Evans rat model affects reward-related behavior and gene regulation (F1) generation unexposed drug. Questions, however, remained regarding potential epigenetic consequences. In current study, using same model, we employed Enhanced Reduced Representation Bisulfite Sequencing interrogate epigenome nucleus accumbens, key brain area involved reward processing. This analysis compared 16 animals with parental THC without characterize relevant systems-level changes DNA methylation. We identified 1027 differentially methylated regions (DMRs) associated F1 adults, each represented by multiple CpGs. These DMRs fell predominantly within introns, exons, intergenic intervals, while showing significant depletion promoters. From these, network DMR-associated genes glutamatergic synaptic regulation, which exhibited altered mRNA expression accumbens. data provide novel insight into drug-related cross-generational serve as useful resource investigators explore neurobiological systems underlying abuse vulnerability.