MDMA (Ecstasy) Decreases the Number of Neurons and Stem Cells in Embryonic Cortical Cultures
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Ecstasy, 3,4-methylenedioxymetamphetamine (MDMA), is a recreational drug used among adolescents, including young pregnant women. MDMA passes the placental barrier and may therefore influence fetal development. The aim was to investigate the direct effect of MDMA on cortical cells using dissociated CNS cortex of rat embryos, E17. The primary culture was exposed to a single dose of MDMA and collected 5 days later. MDMA caused a dramatic, dose-dependent (100 and 400 μM) decrease in nestin-positive stem cell density, as well as a significant reduction (400 μM) in NeuN-positive cells. By qPCR, MDMA (200 μM) caused a significant decrease in mRNA expression of the 5HT3 receptor, dopamine D1 receptor, and glutamate transporter EAAT2-1, as well as an increase in mRNA levels of the NMDA NR1 receptor subunit and the 5HT1A receptor. In conclusion, MDMA caused a marked reduction in stem cells and neurons in embryonic cortical primary cell cultures, which was accompanied by changes in mRNA expression of specific receptors and transporters for glutamatergic and monoaminergic neurotransmitters.
KeywordsMDMA Cell culture Cortex Embryos Neural stem cell Cell death mRNA 5HT3 receptor Dopamine D1 receptor Glutamate transporter
This work was supported by the Swedish Research Council (VR-medicin), the Alcohol Research Council of the Swedish Alcohol Retailing Monopoly (Systembolaget), Gyllenstiernska Krapperupsstiftelsen, Åhlen and Magn. Bergvalls stiftelser, Tore Nilson foundation, and Svenska Läkaresällskapet. Drs. Anna Kindlundh-Högberg and Grzegorz Wicher were supported by the Swedish Brain Foundation (Hjärnfonden). Dr. Chris Pickering was supported first by the AFA Insurance grant for Biomedical Alcohol Research and then by the Swedish Brain Foundation (Hjärnfonden).
- Crawford CA, Williams MT, Kohutek JL, Choi FY, Yoshida ST, McDougall SA, Vorhees CV (2006) Neonatal 3,4-methylenedioxymethamphetamine (MDMA) exposure alters neuronal protein kinase A activity, serotonin and dopamine content, and [35S]GTPgammaS binding in adult rats. Brain Res 1077:178–186CrossRefPubMedGoogle Scholar
- Hernandez-Rabaza V, Dominguez-Escriba L, Barcia JA, Rosel JF, Romero FJ, Garcia-Verdugo JM, Canales JJ (2006) Binge administration of 3, 4-methylenedioxymethamphetamine (“ecstasy”) impairs the survival of neural precursors in adult rat dentate gyrus. Neuropharmacology 51:967–973CrossRefPubMedGoogle Scholar
- Koprich JB, Chen EY, Kanaan NM, Campbell NG, Kordower JH, Lipton JW (2003b) Prenatal 3, 4-methylenedioxymethamphetamine (ecstasy) alters exploratory behavior, reduces monoamine metabolism, and increases forebrain tyrosine hydroxylase fiber density of juvenile rats. Neurotoxicol Teratol 25:509–517CrossRefPubMedGoogle Scholar
- Mordenti J, Chappell W (1989) The use of interspecies scaling in toxicokinetics. In: Yacogi A, Kelley J, Batra V (eds) Toxicokinetics and new drug development. Pergamon Press, New York, pp 42–96Google Scholar
- Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3: RESEARCH0034Google Scholar