title: Sarcosine preconditioning induces ischemic tolerance against global cerebral ischemia.
abstract: Brain ischemic tolerance is an endogenous protective mechanism activated by a preconditioning stimulus that is closely related to N-methyl-d-aspartate receptor (NMDAR). Glycine transporter type 1 (GlyT-1) inhibitors potentiate NMDAR and suggest an alternative strategy for brain preconditioning. The aim of this work was to evaluate the effects of brain preconditioning induced by sarcosine, a GlyT-1 inhibitor, against global cerebral ischemia and its relation to NMDAR. Sarcosine was administered over 7 days (300 or 500 mg/kg/day, ip) before the induction of a global cerebral ischemia model in Wistar rats (male, 8-week-old). It was observed that sarcosine preconditioning reduced cell death in rat hippocampi submitted to cerebral ischemia. Hippocampal levels of glycine were decreased in sarcosine-treated animals, which was associated with a reduction of [(3)H] glycine uptake and a decrease in glycine transporter expression (GlyT-1 and GlyT-2). The expression of glycine receptors and the NR1 and NR2A subunits of NMDAR were not affected by sarcosine preconditioning. However, sarcosine preconditioning reduced the expression of the NR2B subunits of NMDAR. In conclusion, these data demonstrate that sarcosine preconditioning induces ischemic tolerance against global cerebral ischemia and this neuroprotective state is associated with changes in glycine transport and reduction of NR2B-containing NMDAR expression.
authors.affiliation: INCT de Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Avenida Alfredo Balena 190, 30130-100 Belo Horizonte, MG, Brazil; Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Avenida Alfredo Balena, 190, 30130-100 Belo Horizonte, MG, Brazil. Electronic address: pintomcx@gmail.com.
authors.forename: M C X
authors.initials: MC
authors.lastname: Pinto
authors.affiliation: Laboratório de Neurociências, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga 6690, 90610-000 Porto Alegre, RS, Brazil.
authors.forename: F
authors.initials: F
authors.lastname: Simão
authors.affiliation: INCT de Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Avenida Alfredo Balena 190, 30130-100 Belo Horizonte, MG, Brazil; Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Avenida Alfredo Balena, 190, 30130-100 Belo Horizonte, MG, Brazil.
authors.forename: F L P
authors.initials: FL
authors.lastname: da Costa
authors.affiliation: INCT de Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Avenida Alfredo Balena 190, 30130-100 Belo Horizonte, MG, Brazil.
authors.forename: D V
authors.initials: DV
authors.lastname: Rosa
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciência Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: M J N
authors.initials: MJ
authors.lastname: de Paiva
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciência Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: R R
authors.initials: RR
authors.lastname: Resende
authors.affiliation: INCT de Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Avenida Alfredo Balena 190, 30130-100 Belo Horizonte, MG, Brazil.
authors.forename: M A
authors.initials: MA
authors.lastname: Romano-Silva
authors.affiliation: Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, R. Domingos Vieira, 590, Belo Horizonte, MG, Brazil.
authors.forename: M V
authors.initials: MV
authors.lastname: Gomez
authors.affiliation: Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Avenida Alfredo Balena, 190, 30130-100 Belo Horizonte, MG, Brazil. Electronic address: renatogomez2000@yahoo.com.br.
authors.forename: R S
authors.initials: RS
authors.lastname: Gomez
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005998:Glycine / Q000378:metabolism*; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012521:Sarcosine / Q000494:pharmacology*
chemical_list: D050487:Glycine Plasma Membrane Transport Proteins; C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; C493269:Slc6a5 protein, rat; C493266:Slc6a9 protein, rat; D005998:Glycine; D012521:Sarcosine
keywords: brain preconditioning; cerebral ischemia; neuroprotection; neurotransmission and glycine transporter type 1