PPAR-α agonist fenofibrate protects against the damaging effects of MPTP in a rat model of Parkinson's disease
| Autor: | Ronise M. Santiago, Maria Fernanda de Paula Werner, Maria A.B.F. Vital, Claudio Da Cunha, Marcelo M.S. Lima, Fernanda S. Tonin, Janaína K. Barbiero, Suelen Lucio Boschen, Luisa Mota da Silva |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Lipid Peroxides medicine.medical_specialty Time Factors Parkinson's disease Tyrosine 3-Monooxygenase Dopamine Substantia nigra Pharmacology medicine.disease_cause Neuroprotection chemistry.chemical_compound Fenofibrate Internal medicine Avoidance Learning medicine Animals Rats Wistar Swimming Biological Psychiatry Hypolipidemic Agents Superoxide Dismutase business.industry Pars compacta Parkinsonism MPTP MPTP Poisoning medicine.disease Glutathione Corpus Striatum Rats Disease Models Animal Oxidative Stress Endocrinology chemistry Exploratory Behavior Encephalitis business Oxidative stress medicine.drug |
| Zdroj: | Progress in Neuro-Psychopharmacology and Biological Psychiatry. 53:35-44 |
| ISSN: | 0278-5846 |
| DOI: | 10.1016/j.pnpbp.2014.02.009 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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