Transcriptomic configuration of mouse brain induced by adolescent exposure to 3,4-methylenedioxymethamphetamine
- Department of Pathology, Microdissection Genomics Research Center, College of Medicine, Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701 (Korea, Republic of)
- Department of Toxicological Research, National Institute of Toxicological Research, Korea Food and Drug Administration, 194 Tongil-ro, Eunpyung-gu, Seoul 122-704 (Korea, Republic of)
- Cellular and Molecular Toxicology Lab, Korea Institute of Science and Technology, Seoul 130-650 (Korea, Republic of)
- Department of Kidney System, College of Oriental Medicine, Kyung Hee University, Seoul (Korea, Republic of)
- Department of Anesthesiology and Pain Medicine, Kwandong University College of Medicine, Gangneung (Korea, Republic of)
- Department of Pathology, Microdissection Genomics Research Center, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701 (Korea, Republic of)
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.
- OSTI ID:
- 21272558
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 237, Issue 1; Other Information: DOI: 10.1016/j.taap.2009.02.027; PII: S0041-008X(09)00102-1; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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