Transcriptomic configuration of mouse brain induced by adolescent exposure to 3,4-methylenedioxymethamphetamine.
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.
Eun
Jung Woo
JW
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.
Kwack
Seung Jun
SJ
Noh
Ji Heon
JH
Jung
Kwang Hwa
KH
Kim
Jeong Kyu
JK
Bae
Hyun Jin
HJ
Xie
Hongjian
H
Ryu
Jae Chun
JC
Ahn
Young Min
YM
Min
Jin-Hye
JH
Park
Won Sang
WS
Lee
Jung Young
JY
Rhee
Gyu Seek
GS
Nam
Suk Woo
SW
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*
D006213:Hallucinogens; D009419:Nerve Tissue Proteins; D018817:N-Methyl-3,4-methylenedioxyamphetamine