Identification of Post-generation Effect of 3,4-methylenedioxymethamphetamine on the mouse brain by large-scale Gene Expression Analysis
- Identification of Post-generation Effect of 3,4-methylenedioxymethamphetamine on the mouse brain by large-scale Gene Expression Analysis
- 은정우; 곽승준; 노지헌; 정광화; 김정규; 배현진; 사홍건; 류재천; 안영민; 박원상; 이정영; 이규식; 남석우
- 3,4-methylenedioxymethamphetamine; brain; Gene Expression; MDMA; Neurotoxicity; Offspring
- Issue Date
- Toxicology letters
- VOL 195, NO 1, 60-67
- The compound 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a synthetic, psychoactive
drug chemically similar to the stimulant methamphetamine and the hallucinogen mescaline. Accumulated
data has revealed potential toxic effects associated with MDMA on brain serotonin and dopamine
neurons in animal models. However, the relevance of these adverse effects on prenatal exposure to this
drug remains unknown. In this study, we demonstrated that prenatal (F0) exposure to MDMA caused
permanent large-scale transcriptional changes in the brains of the offspring (F1), especially in the cerebral
cortex, by gene expression profiling analysis. The expression analysis of the brain of F1 pups, after
maternal ingestion of MDMA (20 mg/kg MDMA), revealed significant transcriptional changes in both
male and female pups. Supervised analysis resulted in the identification of 804 outlier genes in males
and 1784 outlier genes in females as MDMA-associated genes in the F1 generation. Most of the functional
categories of genes, among the outlier genes, were intracellular signaling pathways, including the
MAPK signaling pathway, Wnt signaling pathway, and neuroactive ligand–receptor interaction pathway.
Although these genes were affected byMDMAexposure in utero, their association with brain dysfunction
requires further investigation. The results of this study suggest that prenatal MDMA exposure may affect
the developing brain.
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