Identification of post-generation effect of 3,4-methylenedioxymethamphetamine on the mouse brain by large-scale gene expression analysis.
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.
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, 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
Park
Won Sang
WS
Lee
Jung Young
JY
Rhee
Gyu Seek
GS
Nam
Suk Woo
SW
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
D018817:N-Methyl-3,4-methylenedioxyamphetamine