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Paeonol Protection Against Intrastriatal 6-Hydroxydopamine Rat Model of Parkinson's Disease Publisher



Ghalami J1 ; Mojarad TB1 ; Mansouri M1 ; Khamse S1 ; Roghani M2
Authors
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Authors Affiliations
  1. 1. Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Neurophysiology Research Center, Shahed University, Tehran, Iran

Source: Basic and Clinical Neuroscience Published:2021


Abstract

Introduction: Parkinson's Disease (PD) presentations comprise frequent movement disorders in the elderly with various symptoms consisting of motor and non-motor complications. Paeonol is a phenolic chemical agent that has shown antioxidant and anti-inflammatory effects in different disorders and promising effects on metabotropic glutamate receptors (mGluR)- and GABAA-mediated neurotransmission. In this research, we tried to show the neuroprotective potential of paeonol in rat PD model induced by intrastriatal 6-hydroxydopamine (6-OHDA). Methods: Rats with intrastriatal 6-OHDA lesioning received with paeonol at a dosage of 100 mg/kg/d for one week. In the end, some biomarkers of oxidative stress, apoptosis, and astrogliosis in nigral and striatal tissues were evaluated in addition to behavioral and Tyrosine Hydroxylase (TH) immunohistochemical analysis. Results: The obtained data showed that paeonol alleviates apomorphine-induced rotations and reduces the delay time to initiate and the total time in the narrow beam test. However, its beneficial behavioral effect vanished after intracerebroventricular administration of mGluR III or GABAA receptor antagonists. Moreover, paeonol significantly restored striatal malondialdehyde, tissue levels of reactive oxygen species, the activity of the protective and vital enzymes consisting of superoxide dismutase and catalase, Glial Fibrillary Acidic Protein (GFAP), DNA fragmentation, phosphor apoptosis signal-regulating kinase 1, and nigral aquaporin 4 with no significant and proper change of nitrite, interleukin-1β, inducible nitric oxide synthase, and angiotensin II. Additionally, paeonol prevented injury and reduced tyrosine hydroxylase-containing neurons in the midbrain nigral tissue. Conclusion: These obtained findings evidently designate neuroprotective property of paeonol in 6-OHDA murine model of PD that is exerted via easing of oxidative stress, apoptosis, astrogliosis, and its advantageous effect is to some extent mediated via mGluR III/GABAA pathway. © 2021 Iran University of Medical Sciences. All rights reserved.
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