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 μg/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.
Keywords: Colchicine, Parkinson’s disease, neuroprotection, anti-apoptotic, rotenone, dopaminergic neurons, efflux system, anti-inflammatory, immunostaining analysis, akinesia
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