Transcriptomic configuration of Mouse Brain induced by adolescent exposure to 3,4-methylenedioxymethamphetamine
- Transcriptomic configuration of Mouse Brain induced by adolescent exposure to 3,4-methylenedioxymethamphetamine
- 은정우; 곽승준; 노지헌; 정광화; 김정규; 배현진; 사홍건; 류재천; 안영민; 민진혜; 박원상; 이정영; 이규식; 남석우
- Transcriptomic configuration; 3,4-methylenedioxymethamphetamine; MDMA; Neurotoxicity; Cerebral cortex; Molecular signature
- Issue Date
- Toxicology and applied pharmacology
- VOL 237, NO 1, 91-101
- 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.
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