title: Identification of post-generation effect of 3,4-methylenedioxymethamphetamine on the mouse brain by large-scale gene expression analysis.
abstract: 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 by MDMA exposure 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.
authors.affiliation: Department of Pathology, Microdissection Genomics Research Center, College of Medicine, The Catholic University of Korea, #505 Banpo-dong, Seocho-gu, Seoul, South Korea.
authors.forename: Jung Woo
authors.initials: JW
authors.lastname: Eun
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Kwack
authors.forename: Ji Heon
authors.initials: JH
authors.lastname: Noh
authors.forename: Kwang Hwa
authors.initials: KH
authors.lastname: Jung
authors.forename: Jeong Kyu
authors.initials: JK
authors.lastname: Kim
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Bae
authors.forename: Hongjian
authors.initials: H
authors.lastname: Xie
authors.forename: Jae Chun
authors.initials: JC
authors.lastname: Ryu
authors.forename: Young Min
authors.initials: YM
authors.lastname: Ahn
authors.forename: Won Sang
authors.initials: WS
authors.lastname: Park
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Gyu Seek
authors.initials: GS
authors.lastname: Rhee
authors.forename: Suk Woo
authors.initials: SW
authors.lastname: Nam
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D040081:Protein Array Analysis
chemical_list: D018817:N-Methyl-3,4-methylenedioxyamphetamine