PMID- 27251371
OWN - NLM
STAT- MEDLINE
DCOM- 20170626
LR  - 20181113
IS  - 1476-3524 (Electronic)
IS  - 1029-8428 (Linking)
VI  - 30
IP  - 1
DP  - 2016 Jul
TI  - Metformin Prevented Dopaminergic Neurotoxicity Induced by 
      3,4-Methylenedioxymethamphetamine Administration.
PG  - 101-9
LID - 10.1007/s12640-016-9633-5 [doi]
AB  - Metformin, a well-known antidiabetic drug, has recently been proposed to promote 
      neurogenesis and to have a neuroprotective effect on the neurodegenerative 
      processes induced by the dopaminergic neurotoxin 
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in models of Parkinson's 
      disease. Interestingly, metformin has antioxidant properties and is involved in 
      regulating the production of cytokines released during the neuroinflammatory 
      process. Several studies have reported that 3,4-methylenedioxymethamphetamine 
      (MDMA), a recreational drug mostly consumed by young adults, produces a 
      persistent loss of dopaminergic neurons in the substantia nigra pars compacta 
      (SNc) and caudate putamen (CPu) of mice. The aim of this study was to investigate 
      the potential neuroprotective effect of metformin against short- and long-term 
      neurotoxicity induced by MDMA and its role on MDMA-induced hyperthermia. Adult 
      mice received metformin (2 x 200 mg/kg, 11-h intervals, administered orally), 
      MDMA (4 x 20 mg/kg, 2-h interval, administered intraperitoneally), or MDMA plus 
      metformin (2 x 200 mg/kg, 1 h before the first MDMA administration and 4 h after 
      the last). On the second and third day, mice were treated with vehicle or 
      metformin (1 x 200 mg/kg) and sacrificed 48 h and 7 days after the last MDMA 
      administration. The neuroprotective effect of metformin on MDMA-induced 
      dopaminergic damage was evaluated by dopamine transporter (DAT) and tyrosine 
      hydroxylase (TH) immunohistochemistry in SNc and CPu. Metformin prevented the 
      MDMA-induced loss of TH-positive neurons in the SNc and TH- and DAT-positive 
      fibers in CPu, both at 48 h and 7 days after the last MDMA administration. These 
      results show that metformin is neuroprotective against the short- and 
      long-lasting dopaminergic neurodegeneration induced by MDMA.
FAU - Porceddu, Pier Francesca
AU  - Porceddu PF
AD  - Department of Biomedical Sciences, Section of Neuropsychopharmacology, University 
      of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy. p.f.porceddu@gmail.com.
FAU - Ishola, Ismail Ogunbayode
AU  - Ishola IO
AD  - Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical 
      Sciences, College of Medicine, University of Lagos, Lagos, Nigeria.
FAU - Contu, Liliana
AU  - Contu L
AD  - Department of Biomedical Sciences, Section of Neuropsychopharmacology, University 
      of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy.
FAU - Morelli, Micaela
AU  - Morelli M
AD  - Department of Biomedical Sciences, Section of Neuropsychopharmacology, University 
      of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy.
AD  - CNR, Institute of Neuroscience, Cagliari, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160601
PL  - United States
TA  - Neurotox Res
JT  - Neurotoxicity research
JID - 100929017
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 9100L32L2N (Metformin)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Body Temperature/drug effects
MH  - Caudate Nucleus/metabolism
MH  - Dopamine Plasma Membrane Transport Proteins/metabolism
MH  - Dopaminergic Neurons/*drug effects
MH  - Male
MH  - Metformin/*pharmacology
MH  - Mice
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*antagonists & inhibitors/*toxicity
MH  - Neuroprotective Agents/*pharmacology
MH  - Putamen/metabolism
MH  - Substantia Nigra/metabolism
MH  - Tyrosine 3-Monooxygenase/metabolism
OTO - NOTNLM
OT  - Caudate putamen
OT  - MDMA
OT  - Neurodegeneration
OT  - Neuroprotection
OT  - Substantia nigra
OT  - Tyrosine hydroxylase
EDAT- 2016/06/03 06:00
MHDA- 2017/06/27 06:00
CRDT- 2016/06/03 06:00
PHST- 2015/08/21 00:00 [received]
PHST- 2016/05/21 00:00 [accepted]
PHST- 2016/05/19 00:00 [revised]
PHST- 2016/06/03 06:00 [entrez]
PHST- 2016/06/03 06:00 [pubmed]
PHST- 2017/06/27 06:00 [medline]
AID - 10.1007/s12640-016-9633-5 [pii]
AID - 10.1007/s12640-016-9633-5 [doi]
PST - ppublish
SO  - Neurotox Res. 2016 Jul;30(1):101-9. doi: 10.1007/s12640-016-9633-5. Epub 2016 Jun 
      1.