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Minocycline Protects Dopaminergic Neurons Against Long-Term Rotenone Toxicity

Published online by Cambridge University Press:  02 December 2014

Khaled Radad*
Affiliation:
Department of Pathology, Faculty of Veterinary Medicine, Assiut University, Assiut, Egypt
Rudolf Moldzio
Affiliation:
Institute for Medical Chemistry, Veterinary Medical University, Vienna, Austria
Wolf-Dieter Rausch
Affiliation:
Institute for Medical Chemistry, Veterinary Medical University, Vienna, Austria
*
Department of Pathology, Faculty of Veterinary Medicine, Assiut University, Assiut 71526, Egypt.
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Abstract

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Background:

In Parkinson's disease, most of current therapies only provide symptomatic treatment and so far there is no drug which directly affects the disease process.

Objectives:

To investigate the neuroprotective effects of minocycline against long-term rotenone toxicity in primary dopaminergic cell cultures.

Methods:

Embryonic mice of 14-days-old were used for preparation of primary dopaminergic cell cultures. On the 6th day in vitro, prepared cultures were treated both with minocycline alone (1, 5, 10 and 20 μM) and concomitantly with rotenone (5 and 20 nM) and minocycline. Cultures were incubated at 37°C for six consecutive days. On Day 12 in vitro culture medium was aspirated and used for measuring lactate dehydrogenase. Cultured cells were fixed in 4% paraformaldhyde and stained immunohistochemically against tyrosine hydroxylase.

Results:

Treatment of cultures with 5 and 20 nM of rotenone significantly decreased the survival of tyrosine hydroxylase immunoreactive neurons by 27 and 31% and increased the release of lactate dehydrogenase into the culture medium by 31 and 236%, respectively compared to untreated controls. Minocycline (1, 5, 10 μM) significantly protected tyrosine hydroxylase immunoreactive neurons by 17, 15 and 19% and 13, 22 and 23% against 5 and 20 nM of rotenone, respectively compared to rotenone-treated cultures. Minocycline (only at 10 μM) significantly decreased the release of lactate dehydrogenase by 79% and 133% against 5 and 20 nM of rotenone, respectively.

Conclusion:

Minocycline has neuroprotective potential against the progressive loss of tyrosine hydroxylase immunoreactive neurons induced by long-term rotenone toxicity in primary dopaminergic cultures.

Résumé:

RÉSUMÉ:Contexte:

Dans la maladie de Parkinson, la plupart des traitements actuels ne sont que symptomatiques et il n’existe toujours pas de médicament qui influence directement le processus morbide.

Objectifs:

Le but de l’étude était d’examiner les effets neuroprotecteurs de la minocycline sur des cellules dopaminergiques en culture primaire contre la toxicité à long terme du roténone.

Méthodes:

Des cellules dopaminergiques ont été prélevées chez des souris âgées de 14 jours et mises en culture primaire. Au sixième jour in vitro, les cultures ont été traitées soit par la minocycline seule (1, 5, 10 et 20 μM) ou par le roténone (5 et 20 ηM) et la minocycline. Les cultures ont été incubées à 37°C pendant six jours consécutifs. Au douzième jour in vitro, le milieu de culture a été aspiré et utilisé pour mesurer la déshydrogénase lactique (LDH). Les cellules cultivées étaient alors fixées dans la paraformaldéhyde à 4% et colorée par immunohistochimie pour révéler la tyrosine-hydroxylase.

Résultats:

Le traitement des cellules par le roténone à 5 et 20 ηM a diminué significativement la survie des neurones contenant de la tyrosine-hydroxylase, soit une diminution de 27% et de 31% respectivement et a augmenté la libération de LDH dans le milieu de culture de 31% et 236% respectivement par rapport aux cultures témoins. La minocycline (1, 5, 10 μM) a protégé de façon significative les neurones contenant de la tyrosine-hydroxylase, soit une protection de 17%, 15% et 19% et de 13%, 22% et 23% contre le roténone à 5 et à 20 ηM respectivement. La minocycline (seulement à 10 μM) a diminué significativement la libération de la LDH de 79% et 133% dans les cultures traitées par le roténone à 5 et à 20 ηM respectivement.

Conclusion:

La minocycline a eu un effet neuroprotecteur contre la perte progressive de neurones contenant de la tyrosine-hydroxylase induite par la toxicité à long terme du roténone dans les cultures primaires de cellules dopaminergiques.

Type
Research Article
Copyright
Copyright © The Canadian Journal of Neurological 2010

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