eISSN: 1509-572x
ISSN: 1641-4640
Folia Neuropathologica
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2/2014
vol. 52
 
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Original article
Neuroprotective effect of rotigotine against complex I inhibitors, MPP+ and rotenone, in primary mesencephalic cell culture

Khaled Radad
,
Dieter Scheller
,
Wolf-Dieter Rausch
,
Heinz Reichmann
,
Gabrielle Gille

Folia Neuropathol 2014; 52 (2): 179-186
Online publish date: 2014/06/30
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Introduction: Dopamine agonists are suggested to be more efficacious in treating Parkinson’s disease (PD) as they have neuroprotective properties in addition to their receptor-related actions.

Aim of the study: The present study was designed to investigate the neuroprotective effects of rotigotine, a D3/D2/D1 dopamine receptor agonist, against the two powerful complex I inhibitors, 1-methyl-4-phenylpyridinium (MPP+) and rotenone, in primary mesencephalic cell culture relevant to PD.

Material and methods: Primary mesencephalic cell cultures were prepared from embryonic mouse mesencephala at gestation day 14. Three sets of cultures were treated with rotigotine alone, rotigotine and MPP+, and rotigotine and rotenone to investigate the effect of rotigotine on the survival of dopaminergic neurons against age-, MPP+- and rotenone-induced cell death. At the end of each treatment, cultures were fixed and stained immunohistochemically against tyrosine hydroxylase (TH). The effect of rotigotine against rotenone-induced reactive oxygen species (ROS) production was measured using CH-H2DCFDA fluorescence dye.

Results: Rotigotine alone did not influence the survival of tyrosine hydroxylase immunoreactive (THir) neurons except at 10 µM, it significantly decreased the number of THir neurons by 40% compared to untreated controls. Treatment of cultures with 0.01 µM rotigotine rescued 10% of THir neurons against MPP+-induced cell death. Rotigotine was also found to significantly rescue 20% of THir neurons at 0.01 µM of rotenone-treated cultures. Using of CH-H2DCFDA fluorescence dye, it was found that rotigotine significantly attenuated ROS production compared to rotenone-treated cultures.

Conclusions: Rotigotine provides minor protection against MPP+ and rescues a significant number of THir neurons against rotenone in primary mesencephalic cell cultures relevant to PD.

keywords:

dopamine agonists, dopaminergic neurons, MPP+, neuroprotection, Parkinson’s disease, rotenone, rotigotine

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