title: Transcriptomic configuration of mouse brain induced by adolescent exposure to 3,4-methylenedioxymethamphetamine.
abstract: The amphetamine derivative (+/-)-3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a synthetic amphetamine analogue used recreationally to obtain an enhanced affiliative emotional response. MDMA is a potent monoaminergic neurotoxin with the potential to damage brain serotonin and/or dopamine neurons. As the majority of MDMA users are young adults, the risk that users may expose the fetus to MDMA is a concern. However, the majority of studies on MDMA have investigated the effects on adult animals. Here, we investigated whether long-term exposure to MDMA, especially in adolescence, could induce comprehensive transcriptional changes in mouse brain. Transcriptomic analysis of mouse brain regions demonstrated significant gene expression changes in the cerebral cortex. Supervised analysis identified 1028 genes that were chronically dysregulated by long-term exposure to MDMA in adolescent mice. Functional categories most represented by this MDMA characteristic signature are intracellular molecular signaling pathways of neurotoxicity, such as, the MAPK signaling pathway, the Wnt signaling pathway, neuroactive ligand-receptor interaction, long-term potentiation, and the long-term depression signaling pathway. Although these resultant large-scale molecular changes remain to be studied associated with functional brain damage caused by MDMA, our observations delineate the possible neurotoxic effects of MDMA on brain function, and have therapeutic implications concerning neuro-pathological conditions associated with MDMA abuse.
authors.affiliation: Department of Pathology, Microdissection Genomics Research Center, College of Medicine, The Catholic University of Korea, #505 Banpo-dong, Seocho-gu, Seoul 137-701, 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: Jin-Hye
authors.initials: JH
authors.lastname: Min
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: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D003423:Critical Period, Psychological; D005260:Female; D020869:Gene Expression Profiling; D006213:Hallucinogens / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism*; D011149:Pons / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018709:Statistics, Nonparametric; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D006213:Hallucinogens; D009419:Nerve Tissue Proteins; D018817:N-Methyl-3,4-methylenedioxyamphetamine