Original article Cabergoline protects dopaminergic neurons against rotenone-induced cell death in primary mesencephalic cell culture

Meinel, Jörn; Radad, Khaled; Rausch, Wolf‐Dieter; Reichmann, Heinz; Gille, Gabriele

doi:10.5114/fn.2015.49972

Cited by 4 publications

(2 citation statements)

References 30 publications

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“…The lack of immediate RONS production during a 4-h rotenone exposure of DA neurons was somewhat surprising. However, similar observations have been reported for other cell types and isolated rat brain mitochondria (Esposti et al, 1999;Meinel et al, 2015;Seyfried et al, 2000). The difference between manganese-and rotenone-elicited RONS production could be due to the fact that rotenone rather specifically inhibits complex I, whereas manganese has been shown to also affect complexes II-IV and other mitochondrial enzymes (Degli Esposti, 1998;Gunter et al, 2010;Zhang et al, 2003Zhang et al, , 2004.…”

Section: Discussionsupporting

confidence: 80%

From the Cover: Manganese and Rotenone-Induced Oxidative Stress Signatures Differ in iPSC-Derived Human Dopamine Neurons

Neely

Davison

Aschner

et al. 2017

Toxicological Sciences

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Parkinson's disease (PD) is the result of complex interactions between genetic and environmental factors. Two chemically distinct environmental stressors relevant to PD are the metal manganese and the pesticide rotenone. Both are thought to exert neurotoxicity at least in part via oxidative stress resulting from impaired mitochondrial activity. Identifying shared mechanism of action may reveal clues towards an understanding of the mechanisms underlying PD pathogenesis. Here we compare the effects of manganese and rotenone in human-induced pluripotent stem cells-derived postmitotic mesencephalic dopamine neurons by assessing several different oxidative stress endpoints. Manganese, but not rotenone caused a concentration and time-dependent increase in intracellular reactive oxygen/nitrogen species measured by quantifying the fluorescence of oxidized chloromethyl 2',7'-dichlorodihydrofluorescein diacetate (DCF) assay. In contrast, rotenone but not manganese caused an increase in cellular isoprostane levels, an indicator of lipid peroxidation. Manganese and rotenone both caused an initial decrease in cellular reduced glutathione; however, glutathione levels remained low in neurons treated with rotenone for 24 h but recovered in manganese-exposed cells. Neurite length, a sensitive indicator of overall neuronal health was adversely affected by rotenone, but not manganese. Thus, our observations suggest that the cellular oxidative stress evoked by these 2 agents is distinct yielding unique oxidative stress signatures across outcome measures. The protective effect of rasagiline, a compound used in the clinic for PD, had negligible impact on any of oxidative stress outcome measures except a subtle significant decrease in manganese-dependent production of reactive oxygen/nitrogen species detected by the DCF assay.

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Section: Discussionsupporting

confidence: 80%

From the Cover: Manganese and Rotenone-Induced Oxidative Stress Signatures Differ in iPSC-Derived Human Dopamine Neurons

Neely

Davison

Aschner

et al. 2017

Toxicological Sciences

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“…Primary mesencephalic cell cultures were prepared from OFI/SPF embryos according to Meinel et al [22]. In brief, embryonic mouse mesencephala were dissected on the 14 th day of gestation and cut into small pieces in a drop of DPBS (Invitrogen, Germany), 2 ml of 0.2% trypsin solution (Invitrogen, Germany) and 2 ml of 0.02% DNase I solution (Roche, Germany) were added and the tissue was subsequently incubated in a water bath at 37 o C for 7 min.…”

Section: Methodsmentioning

confidence: 99%

Rapamycin protects dopaminergic neurons against rotenone-induced cell death in primary mesencephalic cell culture

Radad

Moldzio²,

Rausch³

2015

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Effect of cabergoline alginate nanocomposite on the transgenicDrosophila melanogastermodel of Parkinson’s disease

Khanam

Naz

Ali

et al. 2018

Toxicology Mechanisms and Methods

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Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain. Dopamine agonists help the patients with PD by reversing the dopamine depletion and related motor deficits. In the present work, cabergoline, a potent ergot dopamine agonist, was given in the form of cabergoline alginate nanocomposite (CANC) to the PD model flies to study its effects on climbing ability, activity pattern, life span, lipid peroxidation, glutathione (GSH) content, glutathione-S-transferase (GST) activity, dopamine content, protein carbonyl content, mean gray-scale values, and caspase-3 and caspase-9 activities. Cabergoline alginate nanocomposite was synthesized by adding the cabergoline solution in the warm aqueous solution of sodium alginate; The synthesized CANC was characterized using fourier transform (FTIR) infrared spectroscopy, transmission electron microscopy (TEM), and UV-Visible spectroscopic techniques. The synthesized CANC having the final doses of 1, 2, and 3 μM was supplemented with diet and the flies were allowed to feed on it for 24 days. Cabergoline alginate nanocomposite significantly increases climbing ability, reduces lipid peroxidation, GST activity, protein carbonyl content, caspase 3/9 activity, mean gray-scale values, and increases the GSH as well as dopamine content in a dose-dependent manner. The results of this study suggest that CANC is potent in delaying and reducing the symptoms of PD.

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Original article Cabergoline protects dopaminergic neurons against rotenone-induced cell death in primary mesencephalic cell culture

Abstract: A b s t r a c t

Cited by 4 publications

References 30 publications

From the Cover: Manganese and Rotenone-Induced Oxidative Stress Signatures Differ in iPSC-Derived Human Dopamine Neurons

From the Cover: Manganese and Rotenone-Induced Oxidative Stress Signatures Differ in iPSC-Derived Human Dopamine Neurons

Rapamycin protects dopaminergic neurons against rotenone-induced cell death in primary mesencephalic cell culture

Effect of cabergoline alginate nanocomposite on the transgenicDrosophila melanogastermodel of Parkinson’s disease

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