Could MDMA Promote Stemness Characteristics in Mouse Embryonic Stem Cells via mGlu5 Metabotropic Glutamate Receptors?

Objective: ecstasy, or 3, 4 (±) methylenedioxymethamphetamine (mdma), is a potent neurotoxic drug. one of the mechanisms for its toxicity is the secondary release of glutamate.mouse embryonic stemcells (mescs) express only one glutamate receptor,the metabotropicglutamate receptor 5(mglu5), which is involved in the maintenance andself-renewalof mescs. this study aims to investigate whether mdma could influence self-renewal via the mglu5 receptor in mescs. materials and methods: in this expremental study, we used immunocytochemistry and reverse transcription-polymerase chain reaction (rt-pcr) to determine the presenceofthemglu5receptor in mescs.theexpressionofmglu5wasevaluatedaftermdmawas added to mescs throughout neural precursor cell formation as group 1andduring neural precursor cell differentiationas group 2. thestemness characteristicintreatedmescsbyimmunofluorescenceandflowcytometrywasstudied.finally,caspaseactivity was evaluated by fluorescence staining in the treated group. onewayanovaor repeated measure of anovaaccording to the experimental designwasused for statistical analyses.results: in this study mglu5 expression was shown in mescs. in terms of neuronal differentiation, mdma affected mglu5 expression during neural precursor cell formation(group1)andnotduringneuralprecursordifferentiation(group2).mdma(450µm)induced a significant increment in self-renewal properties in mescs but did notreverse2-methyl-6(phenylethynyl) pyridine (mpep,1 µm), a non-competitive selectivemglu5antagonist.fluorescencestainingwithanti-caspase3showedasignificantincrease in the number of apoptotic cells in the mdmagroup.conclusion: we observed a dual role for mdma on mescs: reduced proliferation and maintenance of self-renewal. the lack of decreasing stemness characteristic in presenceofmpepsuggeststhatmdmamediatesitsrolethroughadifferentmechanismthatrequires further investigation. in conclusion, despite being toxic, mdmamaintainsstemnesscharacteristics.