Abstract
Parkinson’s disease (PD) is associated with higher risk of cognitive impairment that may lead to memory loss, confusion, and decreased attention span. In this study, we have investigated the effect of GW0742, a PPAR-β/δ agonist in rat model of cognitive impairment associated with PD. Bilateral intranigral administration of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) (100 µg/1 µl/side) produced significant cognitive dysfunctions. PPAR-β/δ agonist GW0742 at a dose of 30 and 100 µg/kg showed significant improvement in cognitive impairments caused by MPTP in rat model of PD as evident from passive avoidance and Morris water maze test. MPTP-induced massive oxidative damage and DNA fragmentation was ameliorated by GW0742 treatment as observed after MDA and GSH estimation and TUNEL assay. Tyrosine hydroxylase positive neurons were decreased by 25% of normal control in MPTP group and GW0742 treatment restored tyrosine hydroxylase levels showing neuroprotective nature. Further, we performed physiologically based pharmacokinetic (PBPK) modeling study using GastroPlus to characterize the kinetics of GW0742 in the brain. The predicted amounts of GW0742 in brain suggest that it has the ability to cross the blood brain barrier. This study implicates the involvement of PPAR-β/δ in PD induced cognitive impairment.
Keywords: GastroPlus, GW0742, MPTP, parkinson’s disease, PBPK modeling, PPAR beta.
Current Neurovascular Research
Title:A PPAR-β/δ Agonist is Neuroprotective and Decreases Cognitive Impairment in a Rodent Model of Parkinson’s Disease
Volume: 11 Issue: 2
Author(s): Nihar R. Das, Rahul P. Gangwal, Mangesh V. Damre, Abhay T. Sangamwar and Shyam S. Sharma
Affiliation:
Keywords: GastroPlus, GW0742, MPTP, parkinson’s disease, PBPK modeling, PPAR beta.
Abstract: Parkinson’s disease (PD) is associated with higher risk of cognitive impairment that may lead to memory loss, confusion, and decreased attention span. In this study, we have investigated the effect of GW0742, a PPAR-β/δ agonist in rat model of cognitive impairment associated with PD. Bilateral intranigral administration of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) (100 µg/1 µl/side) produced significant cognitive dysfunctions. PPAR-β/δ agonist GW0742 at a dose of 30 and 100 µg/kg showed significant improvement in cognitive impairments caused by MPTP in rat model of PD as evident from passive avoidance and Morris water maze test. MPTP-induced massive oxidative damage and DNA fragmentation was ameliorated by GW0742 treatment as observed after MDA and GSH estimation and TUNEL assay. Tyrosine hydroxylase positive neurons were decreased by 25% of normal control in MPTP group and GW0742 treatment restored tyrosine hydroxylase levels showing neuroprotective nature. Further, we performed physiologically based pharmacokinetic (PBPK) modeling study using GastroPlus to characterize the kinetics of GW0742 in the brain. The predicted amounts of GW0742 in brain suggest that it has the ability to cross the blood brain barrier. This study implicates the involvement of PPAR-β/δ in PD induced cognitive impairment.
Export Options
About this article
Cite this article as:
Das R. Nihar, Gangwal P. Rahul, Damre V. Mangesh, Sangamwar T. Abhay and Sharma S. Shyam, A PPAR-β/δ Agonist is Neuroprotective and Decreases Cognitive Impairment in a Rodent Model of Parkinson’s Disease, Current Neurovascular Research 2014; 11 (2) . https://dx.doi.org/10.2174/1567202611666140318114037
DOI https://dx.doi.org/10.2174/1567202611666140318114037 |
Print ISSN 1567-2026 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5739 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Research Progress of Mechanisms of Ceftriaxone Associated Nephrolithiasis
Mini-Reviews in Medicinal Chemistry The Role of Anticoagulation in IPF
Current Respiratory Medicine Reviews Pathophysiology of NASH: Perspectives for a Targeted Treatment
Current Pharmaceutical Design Bioactive Polyphenols from Grapes and Wine Emphasized with Resveratrol
Current Pharmaceutical Design Neuroprotective Effects of Quercetin: From Chemistry to Medicine
CNS & Neurological Disorders - Drug Targets Neuroprotective Strategies for Neurological Disorders by Natural Products: An update
Current Neuropharmacology Understanding the Role of Hypoxia Inducible Factor During Neurodegeneration for New Therapeutics Opportunities
Current Neuropharmacology Non-Cardiomyocytes in Heart Regeneration
Current Drug Targets Subcutaneous Immunoglobulins: A Promising Alternative for Immunomodulation?
Current Pharmaceutical Design The Many Roles of Chemokine Receptors in Neurodegenerative Disorders: Emerging New Therapeutical Strategies
Current Medicinal Chemistry Is Bilirubin a Marker of Vascular Disease and/or Cancer and is it a Potential Therapeutic Target?
Current Pharmaceutical Design Hemolysis-Associated Pulmonary Hypertension in Sickle Cell Disease: Global Disruption of the Arginine-Nitric Oxide Pathway
Current Hypertension Reviews Rho Kinase Inhibitors: Potential Treatments for Diabetes and Diabetic Complications
Current Pharmaceutical Design Role of Vitamin E in Cellular Antioxidant Defense
Current Chemical Biology A Perspective on Clinical Islet Transplantation: Past, Present and Developments for Future
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Silencing of MiRNA-126 in Kidney Ischemia Reperfusion is Associated with Elevated SDF-1 Levels and Mobilization of Sca-1+/Lin- Progenitor Cells
MicroRNA Cardiolipin Metabolism and the Role it Plays in Heart Failure and Mitochondrial Supercomplex Formation
Cardiovascular & Hematological Disorders-Drug Targets Safety of Cabergoline in the Management of Pituitary Prolactin-Induced Symptoms with Patients Treated with Atypical Neuroleptics
Current Drug Safety The Role of Fatty Acids in the Regulation of Cerebral Vascular Function and Neuroprotection in Ischemia
CNS & Neurological Disorders - Drug Targets An Overview of Recent Patents on Nanoparticles for Drug Delivery Across the Blood Brain Barrier
Recent Patents on Nanomedicine