Role of L-thyroxin in counteracting rotenone induced neurotoxicity in rats.

A key feature of Parkinson's disease is the dopaminergic neuronal cell loss in the substantia nigra pars compacta. Many triggering pathways have been incriminated in the pathogenesis of this disease including inflammation, oxidative stress, excitotoxicity and apoptosis. Thyroid hormone is an essential agent for the growth and maturation of neurons; moreover, it has variable mechanisms for neuroprotection. So, we tested the efficacy of (L)-thyroxin as a neuroprotectant in rotenone model of Parkinson's disease in rats. Thirty Sprague Dawley rats aged 3 months were divided into 3 equal groups. The first received daily intraperitoneal injections of 0.5% carboxymethyl cellulose (CMC) 3 mL/Kg. The second group received rotenone suspended in 0.5% CMC intraperitoneally at a dose of 3 mg/kg, daily. The third group received the same rotenone regimen subcutaneous l-thyroxine at a dose of 7.5 µg daily. All animals were evaluated regarding locomotor disturbance through blinded investigator who monitored akinesia, catalepsy, tremors and performance in open field test. After 35 days the animals were sacrificed and their brains were immunostained against anti-tyrosine hydroxylase and iba-1. Photomicrographs for coronal sections of the substantia nigra and striatum were taken and analyzed using image J software to evaluate cell count in SNpc and striatal fibers density and number of microglia in the nigrostriatal system. The results were then analyzed statistically. Results showed selective protective effects of thyroxin against rotenone induced neurotoxicity in striatum, however, failed to exert similar protection on SN. Moreover, microglial elevated number in nigrostriatal system that was induced by rotenone injections was diminished selectively in striatum only in the l-thyroxin treated group. One of the possible mechanisms deduced from this work was the selective regulation of microglia in striatal tissues. Thus, this study provides an insight into thyroxin neuroprotection warranting further investigation as therapeutic option for Parkinson's disease patients.

Colchicine protects dopaminergic neurons in a rat model of Parkinson's disease.

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.