Title:Comparable Neuroprotective Effects of Pergolide and Pramipexole on Ferrous Sulfate-Induced Dopaminergic Cell Death in Cell Culture
Volume: 15
Issue: 10
Author(s): Doreen Reichelt, Khaled Radad, Rudolf Moldzio, Wolf-Dieter Rausch, Heinz Reichmann and Gabriele Gille
Affiliation:
Keywords:
Dopamine agonists, ferrous sulfate, neuroprotection, Parkinson’s disease, pergolide, pramipexole.
Abstract: Background: Dopamine agonists are utilized clinically as an initial
treatment in younger Parkinson’s disease patients to delay the side effects associated
with commencement of levodopa medication. These agonists also serveas adjunctive
therapeutics with levodopa to lower the incidence of adverse motor symptoms in
advanced stages of the disease.
Objectives: To compare the neuroprotective effects of the dopamine agonists
pergolide and pramipexole on ferrous sulfate-induced neurotoxicity in dopaminergic
neurons from primary mesencephalic cell culture.
Methods: Pergolide (0.001-1 μM) and pramipexole (0.01-200 μM) were
administered to 8 day primary murine mesencephalic cultures for 24 h. in the presence or absence of
desferal, sulpiride or cycloheximide. Ferrous sulfate (450 μM) was then added for 24 hrs. Lactate
dehydrogenase was assayed in the supernatant, glutathione concentrations measured in cell lysates and
fixed cells were stained for tyrosine hydroxylase.
Results: Ferrous sulphate induced neurotoxity in cultures (p<0.0001) was abolished in the presence of
the iron chelator desferal (p<0.008). Both pergolide (p<0.0001) and pramipexole (p<0.0001)
significantly protected dopaminergic neurons against ferrous sulfate induced neurotoxicity and
pramipexole helped preserve neurite morphology. Pramipexole treatment significantly reduced lactate
dehydrogenase release (p<0.0001) as a measure of cellular injury. The dopamine receptor antagonist
sulpiride (p<0.0001) and the protein synthesis inhibitor cycloheximide (p<0.0001) reduced the
neuroprotective effects of pergolide indicating the involvement receptor stimulation and de novo protein
synthesis in pergolide-mediated neuroprotection. Pramipexole also significantly reversed the decrease in
cellular glutathione concentrations induced by ferrous sulfate (p<0.001).
Conclusion: Both pergolide and pramipexole protect dopaminergic neurons against the neurotoxicity of
ferrous sulfate. Pergolide specifically protects dopaminergic neurons through activation of dopamine
receptors and de novo protein synthesis whereas pramipexole shows an overall effect through an
antioxidant mechanism.
