PMID- 25312280
OWN - NLM
STAT- MEDLINE
DCOM- 20150715
LR  - 20151119
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 89
DP  - 2015 Feb
TI  - Glycine transporters type 1 inhibitor promotes brain preconditioning against 
      NMDA-induced excitotoxicity.
PG  - 274-81
LID - S0028-3908(14)00366-9 [pii]
LID - 10.1016/j.neuropharm.2014.10.003 [doi]
AB  - Brain preconditioning is a protective mechanism, which can be activated by 
      sub-lethal stimulation of the NMDA receptors (NMDAR) and be used to achieve 
      neuroprotection against stroke and neurodegenerative diseases models. Inhibitors 
      of glycine transporters type 1 modulate glutamatergic neurotransmission through 
      NMDAR, suggesting an alternative therapeutic strategy of brain preconditioning. 
      The aim of this work was to evaluate the effects of brain preconditioning induced 
      by NFPS, a GlyT1 inhibitor, against NMDA-induced excitotoxicity in mice 
      hippocampus, as well as to study its neurochemical mechanisms. C57BL/6 mice 
      (male, 10-weeks-old) were preconditioned by intraperitoneal injection of NFPS at 
      doses of 1.25, 2.5 or 5.0 mg/kg, 24 h before intrahippocampal injection of NMDA. 
      Neuronal death was evaluated by fluoro jade C staining and neurochemical 
      parameters were evaluated by gas chromatography-mass spectrometry, scintillation 
      spectrometry and western blot. We observed that NFPS preconditioning reduced 
      neuronal death in CA1 region of hippocampus submitted to NMDA-induced 
      excitotoxicity. The amino acids (glycine and glutamate) uptake and content were 
      increased in hippocampus of animals treated with NFPS 5.0 mg/kg, which were 
      associated to an increased expression of type-2 glycine transporter (GlyT2) and 
      glutamate transporters (EAAT1, EAAT2 and EAAT3). The expression of GlyT1 was 
      reduced in animals treated with NFPS. Interestingly, the preconditioning reduced 
      expression of GluN2B subunits of NMDAR, whereas did not change the expression of 
      GluN1 or GluN2A in all tested doses. Our study suggests that NFPS preconditioning 
      induces resistance against excitotoxicity, which is associated with neurochemical 
      changes and reduction of GluN2B-containing NMDAR expression.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Pinto, Mauro Cunha Xavier
AU  - Pinto MC
AD  - INCT de Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas 
      Gerais, Av. Alfredo Balena 190, 30130-100, Belo Horizonte, MG, Brazil; 
      Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal de Minas 
      Gerais, Av. Alfredo Balena, 190, 30130-100, Belo Horizonte, MG, Brazil. 
      Electronic address: mauroxavier@ufmg.br.
FAU - Lima, Isabel Vieira de Assis
AU  - Lima IV
AD  - Departamento de Farmacologia, Instituto de Ciencia Biologicas, Universidade 
      Federal de Minas Gerais, Av. Antonio Carlos, 6627, 31270-901, Belo Horizonte, MG, 
      Brazil.
FAU - da Costa, Flavia Lage Pessoa
AU  - da Costa FL
AD  - INCT de Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas 
      Gerais, Av. Alfredo Balena 190, 30130-100, Belo Horizonte, MG, Brazil; 
      Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal de Minas 
      Gerais, Av. Alfredo Balena, 190, 30130-100, Belo Horizonte, MG, Brazil.
FAU - Rosa, Daniela Valadao
AU  - Rosa DV
AD  - INCT de Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas 
      Gerais, Av. Alfredo Balena 190, 30130-100, Belo Horizonte, MG, Brazil.
FAU - Mendes-Goulart, Vania Aparecida
AU  - Mendes-Goulart VA
AD  - Departamento de Bioquimica e Imunologia, Instituto de Ciencia Biologicas, 
      Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, 31270-901, Belo 
      Horizonte, MG, Brazil.
FAU - Resende, Rodrigo Ribeiro
AU  - Resende RR
AD  - Departamento de Bioquimica e Imunologia, Instituto de Ciencia Biologicas, 
      Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, 31270-901, Belo 
      Horizonte, MG, Brazil.
FAU - Romano-Silva, Marco Aurelio
AU  - Romano-Silva MA
AD  - INCT de Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas 
      Gerais, Av. Alfredo Balena 190, 30130-100, Belo Horizonte, MG, Brazil.
FAU - de Oliveira, Antonio Carlos Pinheiro
AU  - de Oliveira AC
AD  - Departamento de Farmacologia, Instituto de Ciencia Biologicas, Universidade 
      Federal de Minas Gerais, Av. Antonio Carlos, 6627, 31270-901, Belo Horizonte, MG, 
      Brazil.
FAU - Gomez, Marcus Vinicius
AU  - Gomez MV
AD  - Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, R. Domingos 
      Vieira, 590, Belo Horizonte, MG, Brazil.
FAU - Gomez, Renato Santiago
AU  - Gomez RS
AD  - Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal de Minas 
      Gerais, Av. Alfredo Balena, 190, 30130-100, Belo Horizonte, MG, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141013
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Fluoresceins)
RN  - 0 (Glycine Plasma Membrane Transport Proteins)
RN  - 0 
      (N-(3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)-3-(4'-phenylphenoxy)propyl)sarcosine)
RN  - 0 (fluoro jade)
RN  - 10028-17-8 (Tritium)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - TE7660XO1C (Glycine)
RN  - Z711V88R5F (Sarcosine)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Excitatory Amino Acid Agonists/*toxicity
MH  - Fluoresceins
MH  - Gas Chromatography-Mass Spectrometry
MH  - Gene Expression Regulation/drug effects
MH  - Glutamic Acid/metabolism
MH  - Glycine/metabolism
MH  - Glycine Plasma Membrane Transport Proteins/*antagonists & inhibitors
MH  - Hippocampus/drug effects/injuries
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - N-Methylaspartate/*toxicity
MH  - *Neurotoxicity Syndromes/etiology/pathology/prevention & control
MH  - Sarcosine/administration & dosage/*analogs & derivatives
MH  - Time Factors
MH  - Tritium/metabolism
OTO - NOTNLM
OT  - Brain preconditioning
OT  - Glycine transporter type 1
OT  - Neuroprotection
OT  - Neurotransmission
EDAT- 2014/10/15 06:00
MHDA- 2015/07/16 06:00
CRDT- 2014/10/15 06:00
PHST- 2014/05/20 00:00 [received]
PHST- 2014/09/07 00:00 [revised]
PHST- 2014/10/01 00:00 [accepted]
PHST- 2014/10/15 06:00 [entrez]
PHST- 2014/10/15 06:00 [pubmed]
PHST- 2015/07/16 06:00 [medline]
AID - S0028-3908(14)00366-9 [pii]
AID - 10.1016/j.neuropharm.2014.10.003 [doi]
PST - ppublish
SO  - Neuropharmacology. 2015 Feb;89:274-81. doi: 10.1016/j.neuropharm.2014.10.003. 
      Epub 2014 Oct 13.