PMID- 30871034
OWN - NLM
STAT- MEDLINE
DCOM- 20190626
LR  - 20200225
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 20
IP  - 5
DP  - 2019 Mar 12
TI  - Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed 
      Rats.
LID - 10.3390/ijms20051242 [doi]
LID - 1242
AB  - Several mechanisms underlying 3,4-Methylenedioxy-N-methylamphetamine (MDMA) 
      neurotoxicity have been proposed, including neurochemical alterations and 
      excitotoxicity mediated by reactive oxygen species (ROS), nitric oxide (NO), and 
      reactive nitrogen species (RNS). However, ROS, NO, and RNS sources in the brain 
      are not fully known. We aimed to investigate possible alterations in the 
      expression of the ROS producer NOX enzymes (NOX2, NOX1, and NOX4), NO generators 
      (iNOS, eNOS, and nNOS), markers of oxidative (8-hydroxy-2'-deoxyguanosine, 
      8OHdG), and nitrosative (3-nitrotyrosine, NT) stress, as well as the 
      colocalization between cells positive for the dopamine transporter (DT1) and 
      cells expressing the neuronal nuclei (NeuN) marker, in the frontal cortex of rats 
      receiving saline or MDMA, sacrificed 6 h, 16 h, or 24 h after its administration. 
      MDMA did not affect NOX2, NOX1, and NOX4 immunoreactivity, whereas iNOS 
      expression was enhanced. The number of NT-positive cells was increased in 
      MDMA-exposed animals, whereas no differences were detected in 8OHdG expression 
      among experimental groups. MDMA and NT markers colocalized with DT1 positive 
      cells. DT1 immunostaining was found in NeuN-positive stained cells. Virtually no 
      colocalization was observed with microglia and astrocytes. Moreover, MDMA 
      immunostaining was not found in NOX2-positive cells. Our results suggest that 
      iNOS-derived nitrosative stress, but not NOX enzymes, may have a crucial role in 
      the pathogenesis of MDMA-induced neurotoxicity, highlighting the specificity of 
      different enzymatic systems in the development of neuropathological alterations 
      induced by the abuse of this psychoactive compound.
FAU - Schiavone, Stefania
AU  - Schiavone S
AD  - Department of Clinical and Experimental Medicine, University of Foggia, Via 
      Napoli, 20, 71122 Foggia, Italy. stefania.schiavone@unifg.it.
FAU - Neri, Margherita
AU  - Neri M
AUID- ORCID: 0000-0002-6459-1669
AD  - Department of Morphology, Surgery and Experimental Medicine, University of 
      Ferrara, Via Fossato di Mortara, 70, 44100 Ferrara, Italy. 
      margherita.neri@unife.it.
FAU - Maffione, Angela Bruna
AU  - Maffione AB
AD  - Department of Clinical and Experimental Medicine, University of Foggia, Via 
      Napoli, 20, 71122 Foggia, Italy. angelabruna.maffione@unifg.it.
FAU - Frisoni, Paolo
AU  - Frisoni P
AD  - Department of Morphology, Surgery and Experimental Medicine, University of 
      Ferrara, Via Fossato di Mortara, 70, 44100 Ferrara, Italy. 
      paolo.frisoni@unife.it.
FAU - Morgese, Maria Grazia
AU  - Morgese MG
AD  - Department of Clinical and Experimental Medicine, University of Foggia, Via 
      Napoli, 20, 71122 Foggia, Italy. mariagrazia.morgese@unifg.it.
FAU - Trabace, Luigia
AU  - Trabace L
AD  - Department of Clinical and Experimental Medicine, University of Foggia, Via 
      Napoli, 20, 71122 Foggia, Italy. luigia.trabace@unifg.it.
FAU - Turillazzi, Emanuela
AU  - Turillazzi E
AD  - Section of Legal Medicine, Department of Surgical, Medical, Molecular and 
      Critical Pathology, University of Pisa, Via Roma 55, 56126 Pisa, Italy. 
      emanuela_turillazzi@inwind.it.
LA  - eng
GR  - X5ZIKJ9/Regione Puglia/
GR  - OC970P6/Regione Puglia/
PT  - Journal Article
DEP - 20190312
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Reactive Nitrogen Species)
RN  - 0 (Reactive Oxygen Species)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, rat)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Astrocytes/drug effects/metabolism
MH  - Brain/drug effects/metabolism
MH  - Dopamine Plasma Membrane Transport Proteins/metabolism
MH  - Dopaminergic Neurons/*drug effects/*metabolism
MH  - Male
MH  - Microglia/drug effects/metabolism
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type II/*metabolism
MH  - Nitrosative Stress/*drug effects
MH  - Oxidation-Reduction/drug effects
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Reactive Nitrogen Species/metabolism
MH  - Reactive Oxygen Species/metabolism
PMC - PMC6429174
OTO - NOTNLM
OT  - MDMA
OT  - NADPH oxidases
OT  - iNOS
OT  - nitrosative stress
OT  - oxidative stress
COIS- The authors declare no conflict of interest.
EDAT- 2019/03/16 06:00
MHDA- 2019/06/27 06:00
PMCR- 2019/03/01
CRDT- 2019/03/16 06:00
PHST- 2019/01/03 00:00 [received]
PHST- 2019/02/28 00:00 [revised]
PHST- 2019/03/05 00:00 [accepted]
PHST- 2019/03/16 06:00 [entrez]
PHST- 2019/03/16 06:00 [pubmed]
PHST- 2019/06/27 06:00 [medline]
PHST- 2019/03/01 00:00 [pmc-release]
AID - ijms20051242 [pii]
AID - ijms-20-01242 [pii]
AID - 10.3390/ijms20051242 [doi]
PST - epublish
SO  - Int J Mol Sci. 2019 Mar 12;20(5):1242. doi: 10.3390/ijms20051242.