title: Neuroprotective effects of peroxisome proliferator-activated receptor alpha and gamma agonists in model of parkinsonism induced by intranigral 1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine.
abstract: A large body of evidence suggests that peroxisome proliferator-activated receptor (PPAR) agonists may improve some of the pathological features of Parkinson's disease (PD). In the present study, we evaluated the effects of the PPAR-α agonist fenofibrate (100mg/kg) and PPAR-γ agonist pioglitazone (30mg/kg) in a rat model of parkinsonism induced by intranigral 1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine (MPTP). Male Wistar rats were pretreated with both drugs for 5 days and received an infusion of MPTP. The experiments were divided into two parts. First, 1, 7, 14, and 21 days after surgery, the animals were submitted to the open field test. On days 21 and 22, the rats were subjected to the forced swim test and two-way active avoidance task. In the second part of the study, 24h after neurotoxin administration, immunohistochemistry was performed to assess tyrosine hydroxylase activity. The levels of dopamine and its metabolites in the striatum were determined using high-performance liquid chromatography, and fluorescence detection was used to assess caspase-3 activation in the substantia nigra pars compacta (SNpc). Both fenofibrate as pioglitazone protected against hypolocomotion, depressive-like behavior, impairment of learning and memory, and dopaminergic neurodegeneration caused by MPTP, with dopaminergic neuron loss of approximately 33%. Fenofibrate and pioglitazone also protected against the increased activation of caspase-3, an effector enzyme of the apoptosis cascade that is considered one of the pathological features of PD. Thus, PPAR agonists may contribute to therapeutic strategies in PD.
authors.affiliation: Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, Brazil. Electronic address: janafarma@hotmail.com.
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 M
authors.initials: RM
authors.lastname: Santiago
authors.affiliation: Departamento de Neurologia e Neurocirurgia, Disciplina de Neurologia Experimental, Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil.
authors.forename: Daniele Suzete
authors.initials: DS
authors.lastname: Persike
authors.affiliation: Departamento de Neurologia e Neurocirurgia, Disciplina de Neurologia Experimental, Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: da Silva Fernandes
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: Claudio
authors.initials: C
authors.lastname: da Cunha
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: Lucio Boschen
authors.affiliation: Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, 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.
authors.forename: Maria A B F
authors.initials: MA
authors.lastname: Vital
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D011345:Fenofibrate / Q000627:therapeutic use; D020267:MPTP Poisoning / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D047493:PPAR alpha / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects; D013550:Swimming / Q000523:psychology; D045162:Thiazolidinediones / Q000627:therapeutic use; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D047493:PPAR alpha; D047495:PPAR gamma; D045162:Thiazolidinediones; C059557:dopamine, Gly-Pro-amide-; D014446:Tyrosine 3-Monooxygenase; D053148:Caspase 3; D011345:Fenofibrate; D004298:Dopamine; D000077205:Pioglitazone
keywords: Fenofibrate; Neuroprotection; Parkinson's disease; Pioglitazone