Transcriptomic configuration of mouse brain induced by adolescent exposure to 3,4-methylenedioxymethamphetamine.
Jung Woo Eun, Seung Jun Kwack, Ji Heon Noh, Kwang Hwa Jung, Jeong Kyu Kim, Hyun Jin Bae, Hongjian Xie, Jae Chun Ryu, Young Min Ahn, Jin-Hye Min, Won Sang Park, Jung Young Lee, Gyu-Seek Rhee, Suk Woo Nam
Toxicology and Applied Pharmacology May 15, 2009 DOI: 10.1016/j.taap.2009.02.027 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational animal study (transcriptomic analysis) Peer reviewed |
|---|---|
| Population | Adolescent mice |
| Intervention | MDMA |
| Duration | Long-term exposure |
| Topics | MDMA |
| Key findings | Long-term MDMA exposure in adolescent mice was associated with chronic dysregulation of 1,028 genes in the cerebral cortex, concentrated in neurotoxicity-related signaling pathways such as MAPK, Wnt, neuroactive ligand-receptor interaction, long-term potentiation, and long-term depression. The authors suggest these molecular changes may indicate neurotoxic effects of MDMA, though links to functional brain damage remain to be studied. |
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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 3
- Of mice and men on MDMA: a translational comparison of the neuropsychobiological effects of 3,4-methylenedioxymethamphetamine ('Ecstasy'). Brain Research November 14, 2019
- Increased oxidative-modifications of cytosolic proteins in 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)-exposed rat liver. PROTEOMICS January 2011
- Identification of post-generation effect of 3,4-methylenedioxymethamphetamine on the mouse brain by large-scale gene expression analysis. Toxicology Letters February 24, 2010
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