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- W3020863497 abstract "Abstract The monoamine oxidase metabolite of dopamine, 3,4‐dihydroxyphenylacetaldehyde (DOPAL), is hypothesized to induce neurodegeneration in Parkinson's disease (PD). However, DOPAL's effect on astrocyte function is less well known. Furthermore, the conflicting protective and pathological roles of resting and reactive astrocytes in Parkinson's disease have led to astrocytes being characterized as a double‐edged sword in this disease. Using the Neu7 rat astrocyte cell line as a model of astrocyte behaviour, we aimed to evaluate the effect of DOPAL on astrocyte viability, reactivity and mitochondrial function. Astrocytic production of hydrogen peroxide and nitrite was indicative of reactivity. Mitochondrial function was assessed using extracellular flux analysis with the Seahorse extracellular flux analysis system and mitochondria membrane potential dye. We found that DOPAL significantly reduces Neu7 viability, induces apoptosis, decreases mitochondrial performance and increases oxidative and nitrative stress in a concentration‐dependent manner. This is the first in vitro study showing that DOPAL is directly toxic to astrocytes. We predict that the loss of astrocyte viability and the gain of neurotoxic effects, like the increase in oxidative stress, will have detrimental consequences to neuronal viability. This research supports the hypothesis that DOPAL is a contributing factor to PD progression and provides a basis for future research to elucidate the mechanism of DOPAL‐induced astrocyte toxicity in PD." @default.
- W3020863497 created "2020-05-13" @default.
- W3020863497 creator A5009978283 @default.
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- W3020863497 date "2020-05-16" @default.
- W3020863497 modified "2023-09-30" @default.
- W3020863497 title "Dysregulation of astrocytic mitochondrial function following exposure to a dopamine metabolite: Implications for Parkinson's disease" @default.
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- W3020863497 doi "https://doi.org/10.1111/ejn.14764" @default.
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