title: Atorvastatin Prevents Glutamate Uptake Reduction Induced by Quinolinic Acid Via MAPKs Signaling.
abstract: Statins have been shown to promote neuroprotection in a wide range of neurological disorders. However, the mechanisms involved in such effects of statins are not fully understood. Quinolinic acid (QA) is a neurotoxin that induces seizures when infused in vivo and promotes glutamatergic excitotoxicity in the central nervous system. The aim of this study was to evaluate the putative glutamatergic mechanisms and the intracellular signaling pathways involved in the atorvastatin neuroprotective effects against QA toxicity. Atorvastatin (10 mg/kg) treatment for 7 days prevented the QA-induced decrease in glutamate uptake, but had no effect on increased glutamate release induced by QA. Moreover, atorvastatin treatment increased the phosphorylation of ERK1 and prevented the decrease in Akt phosphorylation induced by QA. Neither atorvastatin treatment nor QA infusion altered glutamine synthetase activity or the levels of phosphorylation of p38(MAPK) or JNK1/2 during the evaluation. Inhibition of MEK/ERK signaling pathway, but not PI3K/Akt signaling, abolished the neuroprotective effect of atorvastatin against QA-induced decrease in glutamate uptake. Our data suggest that atorvastatin protective effects against QA toxicity are related to modulation of glutamate transporters via MAPK/ERK signaling pathway.
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, 88040-900, Brazil. samuelvandresen@yahoo.com.br.|Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso, Boa Esperança, Cuiabá, MT, 78060-900, Brazil. samuelvandresen@yahoo.com.br.
authors.forename: S
authors.initials: S
authors.lastname: Vandresen-Filho
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, 88040-900, Brazil.
authors.forename: W C
authors.initials: WC
authors.lastname: Martins
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, 88040-900, Brazil.
authors.forename: D B
authors.initials: DB
authors.lastname: Bertoldo
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, 88040-900, Brazil.
authors.forename: D K
authors.initials: DK
authors.lastname: Rieger
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, 88040-900, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Maestri
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, 88040-900, Brazil.
authors.forename: R B
authors.initials: RB
authors.lastname: Leal
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, 88040-900, Brazil.
authors.forename: C I
authors.initials: CI
authors.lastname: Tasca
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D017378:Quinolinic Acid / Q000633:toxicity*
chemical_list: D027322:Amino Acid Transport System X-AG; D018698:Glutamic Acid; D000069059:Atorvastatin; D017378:Quinolinic Acid
keywords: Akt; Atorvastatin; ERK; Excitotoxicity; Neuroprotection; Quinolinic acid