Research ReportsFenofibrate promotes neuroprotection in a model of rotenone-induced Parkinson’s diseaseBarbiero, Janaína K.; Ramos, Daniele C.; Boschen, Suelen; Bassani, Taysa; Da Cunha, Cláudio; Vital, Maria A. B. F. Author Information Departamento de Farmacologia, Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Universidade Federal do Paraná, Curitiba, PR, Brazil Received 14 October 2021 Accepted as revised 21 July 2022 Correspondence to Daniele C. Ramos, Departamento de Farmacologia, Universidade Federal do Paraná, Setor de Ciências Biológicas, Av. Francisco H. dos Santos s/n, CEP: 81.531–990, Caixa Postal: 19031, Curitiba, Paraná, Brazil, E-mail: [email protected]; [email protected] Behavioural Pharmacology: December 2022 - Volume 33 - Issue 8 - p 513-526 doi: 10.1097/FBP.0000000000000699 Buy Metrics Abstract Parkinson’s disease is a neurodegenerative disease, the etiology of which remains unknown, but some likely causes include oxidative stress, mitochondrial dysfunction and neuroinflammation. Peroxisome-proliferator-activated receptor (PPAR) agonists have been studied in animal models of Parkinson’s disease and have shown neuroprotective effects. In this study, we aimed to (1) confirm the neuroprotective effects of PPAR-alpha agonist fenofibrate. To this end, male rats received fenofibrate (100 mg/kg) orally for 15 days, 5 days before the intraperitoneal injections of rotenone (2.5 mg/kg for 10 days). After finishing the treatment with rotenone and fenofibrate, animals were subjected to the open field, the forced swim test and the two-way active avoidance task. Subsequently, rats were euthanized for measurement of dopamine and metabolites levels in the striatum and quantification of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra pars compacta (SNpc). In addition, we aimed to (2) evaluate the neuroprotective effects of fenofibrate on the accumulation of α-synuclein aggregates. Here, rats were treated for 5 days with fenofibrate continuing for over 28 days with rotenone. Then, animals were perfused for immunohistochemistry analysis of α-synuclein. The results showed that fenofibrate reduced depressive-like behavior and memory impairment induced by rotenone. Moreover, fenofibrate diminished the depletion of striatal dopamine and protected against dopaminergic neuronal death in the SNpc. Likewise, the administration of fenofibrate attenuated the aggregation of α-synuclein in the SNpc and striatum in the rotenone-lesioned rats. Our study confirmed that fenofibrate exerted neuroprotective effects because parkinsonian rats exhibited reduced behavioral, neurochemical and immunohistochemical changes, and importantly, a lower number of α-synuclein aggregates. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.