MDMA (Ecstasy) decreases the number of neurons and stem cells in embryonic cortical cultures.
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 microM) decrease in nestin-positive stem cell density, as well as a significant reduction (400 microM) in NeuN-positive cells. By qPCR, MDMA (200 microM) caused a significant decrease in mRNA expression of the 5HT3 receptor, dopamine D(1) receptor, and glutamate transporter EAAT2-1, as well as an increase in mRNA levels of the NMDA NR1 receptor subunit and the 5HT(1A) 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.
Kindlundh-Högberg
Anna M S
AM
Department of Neuroscience, Uppsala University, Uppsala, Sweden. Anna.Kindlundh@neuro.uu.se
Pickering
Chris
C
Wicher
Grzegorz
G
Hobér
David
D
Schiöth
Helgi B
HB
Fex Svenningsen
Asa
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology*; D004622:Embryo, Mammalian / Q000166:cytology*; D005786:Gene Expression Regulation / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology
D012333:RNA, Messenger; D053148:Caspase 3; D018817:N-Methyl-3,4-methylenedioxyamphetamine