Impact of Glucocorticoid on a Cellular Model of Parkinson's Disease: Oxidative Stress and Mitochondrial Function.

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2021-08-22

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Claros, Silvia
Gil, Antonio
Martinelli, Mauro
Valverde, Nadia
Lara, Estrella
Boraldi, Federica
Pavia, Jose
Martin-Montañez, Elisa
Garcia-Fernandez, Maria

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MDPI AG
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Abstract

Stress seems to contribute to the neuropathology of Parkinson's disease (PD), possibly by dysregulation of the hypothalamic-pituitary-adrenal axis. Oxidative distress and mitochondrial dysfunction are key factors involved in the pathophysiology of PD and neuronal glucocorticoid-induced toxicity. Animal PD models have been generated to study the effects of hormonal stress, but no in vitro model has yet been developed. Our aim was to examine the impact of corticosterone (CORT) administration on a dopaminergic neuronal cell model of PD induced by the neurotoxin MPP+, as a new combined PD model based on the marker of endocrine response to stress, CORT, and oxidative-mitochondrial damage. We determined the impact of CORT, MPP+ and their co-incubation on reactive oxygen species production (O2-•), oxidative stress cellular markers (advanced-oxidation protein products and total antioxidant status), mitochondrial function (mitochondrial membrane potential and mitochondrial oxygen consumption rate) and neurodegeneration (Fluoro-Jade staining). Accordingly, the administration of MPP+ or CORT individually led to cell damage compared to controls (p < 0.05), as determined by several methods, whereas their co-incubation produced strong cell damage (p < 0.05). The combined model described here could be appropriate for investigating neuropathological hallmarks and for evaluating potential new therapeutic tools for PD patients suffering mild to moderate emotional stress.

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MeSH Terms

Parkinson Disease
Membrane Potential, Mitochondrial
Hypothalamo-Hypophyseal System
Oxidative Stress
Dopaminergic Neurons
Nervous System Diseases
Mitochondria
Antioxidants
Reactive Oxygen Species
Corticosterone
Glucocorticoids
Neurotoxins

DeCS Terms

Técnicas in vitro
Corticosterona
Potencial de la membrana mitocondrial
Células
Consumo de oxígeno
Estrés psicológico
Toxicidad
Enfermedades mitocondriales
Enfermedad de Parkinson
Neuropatología
Glucocorticoides

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Keywords

Parkinson’s disease, hormonal stress, mitochondria, oxidative distress

Citation

Claros S, Gil A, Martinelli M, Valverde N, Lara E, Boraldi F, et al. Impact of Glucocorticoid on a Cellular Model of Parkinson's Disease: Oxidative Stress and Mitochondrial Function. Brain Sci. 2021 Aug 22;11(8):1106.