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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
neuroscience
Colchicine protects dopaminergic neurons in a rat model of Parkinson's disease
CNS and Neurological Disorders - Drug Targets, Volume 11, No. 7, Year 2012
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Description
A key feature of Parkinson's disease is the dopaminergic neuronal cell loss in the substantia nigra pars compacta. Besides inflammation, oxidative stress and apoptosis, a recent hypothesis suggested that degeneration of dopaminergic neurons occurs secondary to abnormal mitosis in these 'postmitotic neurons', ending up in apoptosis. Hence, recent therapies tried to prevent this mitotic cycle in dopaminergic neurons. However, most of the advocated therapies e.g., siRNA-induced silencing of cell cycle regulators, seems far from clinical application. In consequence, the use of anti-mitotic drugs could be a more practical alternative. Colchicine is one clinically approved drug that beyond its anti-mitotic effects has anti-inflammatory, anti-oxidant and anti-apoptotic properties. Moreover, clinical surveys proved that patients receiving colchicine for treating musculoskeletal disorders have lower incidence of Parkinson's disease. In addition, the difficult penetration of colchicines to the blood brain barrier disappears in parkinsonian patients due to depression of the p-glycoprotein efflux system. Based on these clinical data we explored the neuroprotective effects of colchicine in the rat rotenone model of Parkinson's disease. Thirty Sprague Dawley rats aged 3 months were divided into 3 equal groups. The first group received daily intraperitoneal injections of 0.5% carboxymethyl cellulose 3 mL/kg. The second group received rotenone suspended in 0.5% carboxymethyl cellulose intraperitoneally at a dose of 3 mg/kg, daily. The third group received the same rotenone regimen plus daily oral colchicine at a dose of 20 βg/kg. All animals were evaluated regarding locomotor disturbance through a blinded investigator who monitored akinesia, tremors and performance on grid test. After 35 and 70 days the animals were sacrificed and their brains were immunostained against anti-tyrosine hydroxylase. Results showed protective effects of colchicine against rotenone induced neurotoxicity as evident by behavioral tests and immunostaining analysis. Thus, this study provides, for the first time, experimental evidence that colchicine protects against the neurotoxic effects of rotenone on dopaminergic neurons, warranting further investigation as a therapeutic option for Parkinson's disease patients. © 2012 Bentham Science Publishers.
Authors & Co-Authors
Salama, Mohamed M.
Egypt, Mansoura
Faculty of Medicine
Ellaithy, Amr
Egypt, Mansoura
Faculty of Medicine
Helmy, Basem
Egypt, Mansoura
Faculty of Medicine
El-Gamal, Mohamed
Egypt, Mansoura
Faculty of Medicine
Tantawy, Dina
Egypt, Mansoura
Faculty of Medicine
Mohamed, Mie Ali
Egypt, Mansoura
Faculty of Medicine
Sheashaa, Hussein Atia
Egypt, Mansoura
Mansoura University, Urology and Nephrology Center
Sobh, Mohamed Abdel Kader
Egypt, Mansoura
Faculty of Medicine
Egypt, Mansoura
Mansoura University, Urology and Nephrology Center
Arias-Carrion, Oscar
Mexico, Mexico
Hospital General Dr. Manuel Gea González
Statistics
Citations: 20
Authors: 9
Affiliations: 3
Identifiers
Doi:
10.2174/1871527311201070836
ISSN:
18715273
e-ISSN:
19963181
Research Areas
Cancer
Health System And Policy
Mental Health
Study Design
Cross Sectional Study
Cohort Study