PMID- 23508940
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130320
LR  - 20211021
IS  - 2228-5806 (Print)
IS  - 2228-5814 (Electronic)
IS  - 2228-5806 (Linking)
VI  - 14
IP  - 3
DP  - 2012 Fall
TI  - Could MDMA Promote Stemness Characteristics in Mouse Embryonic Stem Cells via 
      mGlu5 Metabotropic Glutamate Receptors?
PG  - 185-92
AB  - 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 stem cells (mESCs) express only one glutamate 
      receptor, the metabotropic glutamate receptor 5 (mGlu5), which is involved in the 
      maintenance and self-renewal of 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 presence of the 
      mGlu5 receptor in mESCs. The expression of mGlu5 was evaluated after MDMA was 
      added to mESCs throughout neural precursor cell formation as group 1 and during 
      neural precursor cell differentiation as group 2. The stemness characteristic in 
      treated mESCs by immunofluorescence and flow cytometry was studied. Finally, 
      caspase activity was evaluated by fluorescence staining in the treated group. 
      One-way ANOVA or repeated measure of ANOVA according to the experimental design 
      was used 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 (group 1) and not during neural 
      precursor differentiation (group 2). MDMA (450 microM) induced a significant 
      increment in self-renewal properties in mESCs but did not reverse 
      2-methyl-6(phenylethynyl) pyridine (MPEP, 1 microM), a non-competitive selective 
      mGlu5 antagonist. Fluorescence staining with anti-caspase 3 showed a significant 
      increase in the number of apoptotic cells in the MDMA group. CONCLUSION: WE 
      OBSERVED A DUAL ROLE FOR MDMA ON MESCS: reduced proliferation and maintenance of 
      self-renewal. The lack of decreasing stemness characteristic in presence of MPEP 
      suggests that MDMA mediates its role through a different mechanism that requires 
      further investigation. In conclusion, despite being toxic, MDMA maintains 
      stemness characteristics.
FAU - Meamar, Rokhsareh
AU  - Meamar R
AD  - 1. Department of Cell and Molecular Biology, Cell Science Research Center, Royan 
      Institute for Animal Biotechnology, ACECR, Isfahan, Iran ; 2. Isfahan 
      Neurosciences research center, Isfahan University of Medical Sciences, Isfahan, 
      Iran ; 3. Islamic Azad University, Najafabad Branch, Isfahan, Iran.
FAU - Karamali, Fereshte
AU  - Karamali F
FAU - Mousavi, Seyed Ali
AU  - Mousavi SA
FAU - Baharvand, Hossein
AU  - Baharvand H
FAU - Nasr-Esfahani, Mohammad Hossein
AU  - Nasr-Esfahani MH
LA  - eng
PT  - Journal Article
DEP - 20121212
PL  - Iran
TA  - Cell J
JT  - Cell journal
JID - 101566618
PMC - PMC3584439
OTO - NOTNLM
OT  - Ecstasy
OT  - Embryonic Stem Cells
OT  - MDMA
OT  - Self Renewal
OT  - mGlu Receptor
EDAT- 2013/03/20 06:00
MHDA- 2013/03/20 06:01
PMCR- 2012/09/01
CRDT- 2013/03/20 06:00
PHST- 2011/12/20 00:00 [received]
PHST- 2012/07/07 00:00 [accepted]
PHST- 2013/03/20 06:00 [entrez]
PHST- 2013/03/20 06:00 [pubmed]
PHST- 2013/03/20 06:01 [medline]
PHST- 2012/09/01 00:00 [pmc-release]
PST - ppublish
SO  - Cell J. 2012 Fall;14(3):185-92. Epub 2012 Dec 12.