7-Fluoro-1,3-diphenylisoquinoline reverses motor and non-motor symptoms induced by MPTP in mice: Role of striatal neuroinflammation
Autor: | Tuane Bazanella Sampaio, Ana Paula Pesarico, Anderson C. Mantovani, Marcel Henrique Marcondes Sari, Cristina W. Nogueira, Gilson Zeni |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Male Parkinson's disease Tyrosine 3-Monooxygenase Striatum Pharmacology Motor Activity Antiparkinson Agents 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Medicine Animals Neuroinflammation biology Tyrosine hydroxylase Behavior Animal business.industry MPTP Dopaminergic Anti-Inflammatory Agents Non-Steroidal Recognition Psychology medicine.disease Isoquinolines Mice Inbred C57BL Neostriatum 030104 developmental biology chemistry 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine Myeloperoxidase biology.protein Antidepressant business 030217 neurology & neurosurgery |
Zdroj: | European journal of pharmacology. 819 |
ISSN: | 1879-0712 |
Popis: | 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. |
Databáze: | OpenAIRE |
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