title: MK-801 alters Na+, K+-ATPase activity and oxidative status in zebrafish brain: reversal by antipsychotic drugs.
abstract: Schizophrenia is a debilitating mental disorder with a global prevalence of 1% and its etiology remains poorly understood. In the current study we investigated the influence of antipsychotic drugs on the effects of MK-801 administration, which is a drug that mimics biochemical changes observed in schizophrenia, on Na(+), K(+)-ATPase activity and some parameters of oxidative stress in zebrafish brain. Our results showed that MK-801 treatment significantly decreased Na(+), K(+)-ATPase activity, and all antipsychotics tested prevented such effects. Acute MK-801 treatment did not alter reactive oxygen/nitrogen species by 2'7'-dichlorofluorscein (H2DCF) oxidation assay, but increased the levels of thiobarbituric acid reactive substances (TBARS), when compared with controls. Some antipsychotics such as sulpiride, olanzapine, and haloperidol prevented the increase of TBARS caused by MK-801. These findings indicate oxidative damage might be a mechanism involved in the decrease of Na(+), K(+)-ATPase activity induced by MK-801. The parameters evaluated in this study had not yet been tested in this animal model using the MK-801, suggesting that zebrafish is an animal model that can contribute for providing information on potential treatments and disease characteristics.
authors.affiliation: Programa de Pós-Graduação em Biologia Celular e Molecular Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681 Porto Alegre, RS 90619-900, Brazil.
authors.forename: Kelly Juliana
authors.initials: KJ
authors.lastname: Seibt
authors.forename: Renata
authors.initials: R
authors.lastname: da Luz Oliveira
authors.forename: Denis Broock
authors.initials: DB
authors.lastname: Rosemberg
authors.forename: Luiz Eduardo Baggio
authors.initials: LE
authors.lastname: Savio
authors.forename: Emilene B S
authors.initials: EB
authors.lastname: Scherer
authors.forename: Felipe
authors.initials: F
authors.lastname: Schmitz
authors.forename: Angela T S
authors.initials: AT
authors.lastname: Wyse
authors.forename: Carla Denise
authors.initials: CD
authors.lastname: Bonan
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D005452:Fluoresceins / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism; D000077152:Olanzapine; D018384:Oxidative Stress / Q000187:drug effects*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D015027:Zebrafish / Q000378:metabolism*
chemical_list: C110400:2',7'-dichlorodihydrofluorescein diacetate; D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D005452:Fluoresceins; D009419:Nerve Tissue Proteins; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D001569:Benzodiazepines; D016291:Dizocilpine Maleate; D013469:Sulpiride; D000254:Sodium-Potassium-Exchanging ATPase; D006220:Haloperidol; D000077152:Olanzapine