Dysregulation of astrocytic mitochondrial function following exposure to a dopamine metabolite: Implications for Parkinson's disease.
Eur J Neurosci
; 53(9): 2960-2972, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-32353182
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.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Dopamina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Eur J Neurosci
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Irlanda