title: In vitro 6-hydroxydopamine-induced toxicity in striatal, cerebrocortical and hippocampal slices is attenuated by atorvastatin and MK-801.
abstract: Parkinson's disease (PD) involves the loss of striatal dopaminergic neurons, although other neurotransmitters and brain areas are also involved in its pathophysiology. In rodent models to PD it has been shown statins improve cognitive and motor deficits and attenuate inflammatory responses evoked by PD-related toxins. Statins are the drugs most prescribed to hypercholesterolemia, but neuroprotective effects have also been attributed to statins treatment in humans and in animal models. This study aimed to establish an in vitro model of 6-hydroxydopamine (6-OHDA)-induced toxicity, used as an initial screening test to identify effective drugs against neural degeneration related to PD. The putative neuroprotective effect of atorvastatin against 6-OHDA-induced toxicity in rat striatal, cerebrocortical and hippocampal slices was also evaluated. 6-OHDA (100μM) decreased cellular viability in slices obtained from rat cerebral cortex, hippocampus and striatum. 6-OHDA also induced an increased reactive oxygen species (ROS) production and mitochondrial dysfunction. Co-incubation of 6-OHDA with atorvastatin (10μM) or MK-801 (50μM) an N-methyl-d-aspartate (NMDA) receptor antagonist, partially attenuated the cellular damage evoked by 6-OHDA in the three brain areas. Atorvastatin partially reduced ROS production in the hippocampus and striatum and disturbances of mitochondria membrane potential in cortex and striatum. 6-OHDA-induced toxicity in vitro displays differences among the brain structures, but it is also observed in cerebrocortical and hippocampal slices, besides striatum.
authors.affiliation: Programa de Pós-graduação em Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Caio M
authors.initials: CM
authors.lastname: Massari
authors.affiliation: Programa de Pós-graduação em Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Adalberto A
authors.initials: AA
authors.lastname: Castro
authors.affiliation: Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Tharine
authors.initials: T
authors.lastname: Dal-Cim
authors.affiliation: Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Débora
authors.initials: D
authors.lastname: Lanznaster
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900 Florianópolis, SC, Brazil. Electronic address: carla.tasca@ufsc.br.
authors.forename: Carla I
authors.initials: CI
authors.lastname: Tasca
mesh_terms: D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000633:toxicity*; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D016291:Dizocilpine Maleate; D016627:Oxidopamine; D000069059:Atorvastatin
keywords: 6-hydroxydopamine; Atorvastatin; Brain slices; Mk-801; Neuroprotection; Parkinson's disease; Toxicity