Genome-Wide DNA Methylation Profiling Reveals Epigenetic Changes in the Rat Nucleus Accumbens Associated With Cross-Generational Effects of Adolescent THC Exposure.
Corey T Watson, Henrietta Szutorisz, Paras Garg, Qammarah Martin, Joseph A Landry, Andrew J Sharp, Yasmin L. Hurd
Neuropsychopharmacology December 2015 DOI: 10.1038/npp.2015.155 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational animal study Peer reviewed |
|---|---|
| Sample size | 32 |
| Population | F1 adult Long-Evans rats: 16 with parental adolescent THC exposure and 16 without |
| Intervention | Δ(9)-tetrahydrocannabinol (THC) |
| Measures | Enhanced Reduced Representation Bisulfite Sequencing, DNA methylation, mRNA expression |
| Topics | Cannabis |
| Key findings | Parental adolescent THC exposure in rats was associated with 1027 differentially methylated regions in the F1 generation's nucleus accumbens, predominantly in introns, exons, and intergenic intervals and depleted at gene promoters. A network of these DMR-associated genes involved in glutamatergic synaptic regulation also showed altered mRNA expression, which the authors propose may represent a cross-generational epigenetic mechanism relevant to drug abuse vulnerability. |
Abstract
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 for drug exposure to even impact subsequent generations. Our previous work demonstrated that adolescent exposure to Δ(9)-tetrahydrocannabinol (THC), the main psychoactive component of marijuana (Cannabis sativa), in a Long-Evans rat model affects reward-related behavior and gene regulation in the subsequent (F1) generation unexposed to the drug. Questions, however, remained regarding potential epigenetic consequences. In the current study, using the same rat model, we employed Enhanced Reduced Representation Bisulfite Sequencing to interrogate the epigenome of the nucleus accumbens, a key brain area involved in reward processing. This analysis compared 16 animals with parental THC exposure and 16 without to characterize relevant systems-level changes in DNA methylation. We identified 1027 differentially methylated regions (DMRs) associated with parental THC exposure in F1 adults, each represented by multiple CpGs. These DMRs fell predominantly within introns, exons, and intergenic intervals, while showing a significant depletion in gene promoters. From these, we identified a network of DMR-associated genes involved in glutamatergic synaptic regulation, which also exhibited altered mRNA expression in the nucleus accumbens. These data provide novel insight into drug-related cross-generational epigenetic effects, and serve as a useful resource for investigators to explore novel neurobiological systems underlying drug abuse vulnerability.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 7
- DNA methylation and the opposing NMDAR dysfunction in schizophrenia and major depression disorders: a converging model for the therapeutic effects of psychedelic compounds in the treatment of psychiatric illness. Molecular Psychiatry November 1, 2023
- Perturbation of 3D nuclear architecture, epigenomic dysregulation and aging, and cannabinoid synaptopathy reconfigures conceptualization of cannabinoid pathophysiology: part 1–aging and epigenomics Frontiers in Psychiatry September 5, 2023
- Regulation of neural connectivity and oscillations by cannabinoids: A review. Neuroscience & Biobehavioral Reviews September 7, 2026
- Consensus paper of the WFSBP task force on cannabis, cannabinoids and psychosis The World Journal of Biological Psychiatry March 22, 2022
- Cannabis and synaptic reprogramming of the developing brain. Nature Reviews Neuroscience July 2021
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