title: PPAR-α agonist fenofibrate protects against the damaging effects of MPTP in a rat model of Parkinson's disease.
abstract: Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The etiology and pathogenesis of PD are still unknown, however, many evidences suggest a prominent role of oxidative stress, inflammation, apoptosis, mitochondrial dysfunction and proteosomal dysfunction. The peroxisome proliferator-activated receptor (PPAR) ligands, a member of the nuclear receptor family, have anti-inflammatory activity over a variety of rodent's models for acute and chronic inflammation. PPAR-α agonists, a subtype of the PPAR receptors, such as fenofibrate, have been shown a major role in the regulation of inflammatory processes. Animal models of PD have shown that neuroinflammation is one of the most important mechanisms involved in dopaminergic cell death. In addition, anti-inflammatory drugs are able to attenuate toxin-induced parkinsonism. In this study we evaluated the effects of oral administration of fenofibrate 100mg/kg 1h after infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the SNpc. First, we assessed the motor behavior in the open field for 24h, 7, 14 and 21 days after MPTP. Twenty-two days after surgery, the animals were tested for two-way active avoidance and forced swimming for evaluation regarding cognitive and depressive parameters, respectively. Twenty-three days after infusion of the toxin, we quantified DA and turnover and evaluated oxidative stress through the measurement of GSH (glutathione peroxidase), SOD (superoxide dismutase) and LOOH (hydroperoxide lipid). The data show that fenofibrate was able to decrease hypolocomotion caused by MPTP 24h after injury, depressive-like behavior 22 days after the toxin infusion, and also protected against decreased level of DA and excessive production of reactive oxygen species (ROS) 23 days after surgery. Thus, fenofibrate has shown a neuroprotective effect in the MPTP model of Parkinson's disease.
authors.affiliation: Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, Brazil.
authors.forename: Janaína K
authors.initials: JK
authors.lastname: Barbiero
authors.affiliation: Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, Brazil.
authors.forename: Ronise
authors.initials: R
authors.lastname: Santiago
authors.affiliation: Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, Brazil.
authors.forename: Fernanda S
authors.initials: FS
authors.lastname: Tonin
authors.affiliation: Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, Brazil.
authors.forename: Suelen
authors.initials: S
authors.lastname: Boschen
authors.affiliation: Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, Brazil.
authors.forename: Luísa Mota
authors.initials: LM
authors.lastname: da Silva
authors.affiliation: Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, Brazil.
authors.forename: Maria Fernanda de Paula
authors.initials: MF
authors.lastname: Werner
authors.affiliation: Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, Brazil.
authors.forename: Claudio
authors.initials: C
authors.lastname: da Cunha
authors.affiliation: Laboratório de Neurofisiologia, Departamento de Fisiologia, Universidade Federal do Paraná, PR, Brazil.
authors.forename: Marcelo M S
authors.initials: MM
authors.lastname: Lima
authors.affiliation: Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, Brazil. Electronic address: vital@ufpr.br.
authors.forename: Maria A B F
authors.initials: MA
authors.lastname: Vital
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004660:Encephalitis / Q000209:etiology* / Q000517:prevention & control*; D005106:Exploratory Behavior / Q000187:drug effects; D011345:Fenofibrate / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008054:Lipid Peroxides / Q000378:metabolism; D020267:MPTP Poisoning / Q000150:complications*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013550:Swimming; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000960:Hypolipidemic Agents; D008054:Lipid Peroxides; D014446:Tyrosine 3-Monooxygenase; D013482:Superoxide Dismutase; D005978:Glutathione; D011345:Fenofibrate; D004298:Dopamine
keywords: Dopamine; Fenofibrate; MPTP; PPAR-α; Parkinson's disease