title: Decreased forelimb ability in mice intracerebroventricularly injected with low dose 6-hydroxidopamine: A model on the dissociation of bradykinesia from hypokinesia.
abstract: Bradykinesia and hypokinesia represent well-known motor symptoms of Parkinson's disease (PD). While bradykinesia (slow execution of movements) is present in less affected PD patients and aggravates as the disease severity increases, hypokinesia (reduction of movement) seems to emerge prominently only in the more affected patients. Here we developed a model based on the central infusion of low dose (40μg) 6-hydroxydopamine (6-OHDA) in mice in an attempt to discriminate bradykinesia (accessed through forelimb inability) from hypokinesia (accessed through locomotor and exploratory activities). The potential beneficial effects of succinobucol against 6-OHDA-induced forelimb inability were also evaluated. One week after the beginning of treatment with succinobucol (i.p. injections, 10mg/kg/day), mice received a single i.c.v. infusion of 6-OHDA (40μg/site). One week after 6-OHDA infusion, general locomotor/exploratory activities (open field test), muscle strength (grid test), forelimb skill (single pellet task), as well as striatal biochemical parameters related to oxidative stress and cellular homeostasis (glutathione peroxidase, glutathione reductase and NADH dehydrogenases activities, lipid peroxidation and TH levels), were evaluated. 6-OHDA infusions did not change locomotor/exploratory activities and muscle strength, as well as the evaluated striatal biochemical parameters. However, 6-OHDA infusions caused significant reductions (50%) in the single pellet reaching task performance, which detects forelimb skill inability and can be used to experimentally identify bradykinesia. Succinobucol partially protected against 6-OHDA-induced forelimb inability. The decreased forelimb ability with no changes in locomotor/exploratory behavior indicates that our 6-OHDA-based protocol represents a useful tool to mechanistically study the dissociation of bradykinesia and hypokinesia in PD.
authors.affiliation: Programa de Pós-Graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88040900 Florianópolis, Santa Catarina, Brazil; Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88040900 Florianópolis, Santa Catarina, Brazil; Departamento Acadêmico de Saúde e Serviço, Instituto Federal de Santa Catarina, 88020030 Florianópolis, Santa Catarina, Brazil.
authors.forename: Renata Pietsch
authors.initials: RP
authors.lastname: Ribeiro
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88040900 Florianópolis, Santa Catarina, Brazil.
authors.forename: Danúbia Bonfanti
authors.initials: DB
authors.lastname: Santos
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88040900 Florianópolis, Santa Catarina, Brazil.
authors.forename: Dirleise
authors.initials: D
authors.lastname: Colle
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88040900 Florianópolis, Santa Catarina, Brazil.
authors.forename: Aline Aita
authors.initials: AA
authors.lastname: Naime
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88040900 Florianópolis, Santa Catarina, Brazil.
authors.forename: Cinara Ludvig
authors.initials: CL
authors.lastname: Gonçalves
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88040900 Florianópolis, Santa Catarina, Brazil.
authors.forename: Heloisa
authors.initials: H
authors.lastname: Ghizoni
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil.
authors.forename: Mariana Appel
authors.initials: MA
authors.lastname: Hort
authors.affiliation: Escola de Química e Alimentos, Universidade Federal de Rio Grande, Campus Santo Antônio da Patrulha, Rio Grande do Sul, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Godoi
authors.affiliation: Departamento de Biologia Celular, Embriologia e Genética, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Paulo Fernando
authors.initials: PF
authors.lastname: Dias
authors.affiliation: Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Antonio Luiz
authors.initials: AL
authors.lastname: Braga
authors.affiliation: Programa de Pós-Graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88040900 Florianópolis, Santa Catarina, Brazil; Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88040900 Florianópolis, Santa Catarina, Brazil. Electronic address: marcelo.farina@ufsc.br.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farina
mesh_terms: D018663:Adrenergic Agents / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D005552:Forelimb / Q000503:physiopathology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D018476:Hypokinesia / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology*; D007276:Injections, Intraventricular; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D053580:Muscle Strength / Q000187:drug effects; D016627:Oxidopamine / Q000008:administration & dosage*; D010446:Peptide Fragments / Q000378:metabolism; D011341:Probucol / Q000008:administration & dosage / Q000031:analogs & derivatives; D011597:Psychomotor Performance / Q000187:drug effects; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D018663:Adrenergic Agents; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D017392:Thiobarbituric Acid Reactive Substances; C106359:glutathione reductase (436-459); D016627:Oxidopamine; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; C471047:succinobucol; D011341:Probucol
keywords: 6-Hydroxidopamine; Bradykinesia; Hypokinesia; Locomotor activity; Parkinson’s disease; Single pellet test