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Parkinson's disease (PD) is a dopaminergic neurodegenerative disorder, which presents motor and non-motor symptoms. 7-Fluoro-1,3-diphenylisoquinoline (FDPI) is an isoquinoline compound with antioxidant and antidepressant properties. This study investigated whether FDPI reverses motor and non-motor symptoms in an acute mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). It was also assessed the anti-inflammatory mechanisms in FDPI pharmacological action. C57Bl/6 male adult mice received four MPTP (20mg/kg, intraperitoneal) or saline (vehicle) injections to induce an acute PD model. FDPI (10mg/kg, intragastric) was daily administered to mice from the 2nd to 9th day after the induction and mice performed the behavioral tests on the 8th and 9th days. Striatum samples were collected for biochemical and molecular analyses. The results of the rotarod and challenging beam tests demonstrated that the administration of FDPI attenuated the impairments in balance and coordination of mice induced by MPTP. The FDPI reversed the short-term memory deficit and depressive-like behavior induced by MPTP in mice. FDPI attenuated the reduction in the striatal tyrosine hydroxylase levels, and it reversed the increase in the cyclooxygenase-2 levels and myeloperoxidase activity caused by MPTP in mice. Therefore, FDPI reversed motor and non-motor symptoms induced by an acute PD model and its restorative effects seem to be mediated by an anti-inflammatory action associated with a modulation of the striatal cyclooxygenase-2 levels and myeloperoxidase activity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Parkinson's disease is a progressive neurodegenerative disorder characterized by degeneration of nigrostriatal dopaminergic neurons. Diphenyl diselenide [(PhSe) 2 ] is a compound with pharmacological proprieties, such as antidepressant and neuroprotective. Therefore, this study investigated whether (PhSe) 2 reverses motor impairment and neurochemical alterations in a model of Parkinson's disease induced by 6-hydroxydopamine (6-OHDA) in rats. For this, male Wistar rats received 20μg/3μl of 6-OHDA or vehicle into the right striatum. Three weeks later, animals were subjected to rotational behavioral test induced by D-amphetamine and randomly divided into four groups: Sham; (PhSe) 2 ; 6-OHDA and 6-OHDA+(PhSe) 2 . The rats received (PhSe) 2 (1mg/kg/day; i.g.) or vehicle (canola oil) during 30 days. After treatment, behavioral tests were performed in order to evaluate the motor function and the ipsilateral striatal tissue was collected for immunoblotting assay. (PhSe) 2 treatment restored the normal motor behavior of 6-OHDA-infused rats in the cylinder, stepping and bridge tests, but not in the rotarod test. The 6-OHDA infusion and/or (PhSe) 2 treatment did not alter the muscle strength and spontaneous locomotion in the forelimb support and open-field tests, respectively. Additionally, striatal brain-derived neurotrophic factor (BDNF), proBDNF and tyrosine hydroxylase (TH) levels of 6-OHDA-lesioned rats were decreased, while the tropomyosin-related kinase B (TrkB) levels were increased. (PhSe) 2 treatment restored striatal proBDNF, TrkB and TH levels. Thus, (PhSe) 2 treatment reversed some motor impairment and TH levels in a 6-OHDA model of Parkinson's disease in rats, demonstrating a potential neurorestorative role. Additionally, the BDNF/TrkB signaling recovery can be involved in its neurorestorative effect., (Copyright © 2016 Elsevier B.V. All rights reserved.)