Non Animal Testing Database

Neurotoxic mechanisms in differentiated neuroblastoma cells

Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Parkinson's disease is a devastating neurodegenerative disorder characterized by a massive loss of dopaminergic neurons that leads to motor and cognitive decline and, ultimately, death. Despite big efforts in developing therapeutic strategies against this disease, there is no effective cure. A major concern in Parkinson's research is the lack of human in vitro models that can facilitate drug screening and the study of molecular mechanisms in an easy and cost-effective way. In this study, a human neuroblastoma cell line is characterized undifferentiated and after differentiation with retinoic acid and compared after treatment with the neurotoxic compound 6-hydroxydopamine. The results show that differentiated cells had characteristics related to neuronal phenotypes with dopaminergic features. When treated with 6-hydroxydopamine, differentiated cells were more sensitive to toxicity, although having higher basal resistance to oxidative stress. Moreover, the inhibition of dopamine transporter was protective only for differentiated cells. In summary, the researchers demonstrate that undifferentiated and differentiated human neuroblastoma cells have distinct phenotypes with different features and react differently to toxic compounds. Additionally, the data presented here support the use of retinoic acid differentiated cells as an in vitro platform to study pathological mechanisms and develop new therapeutical approaches for Parkinson's disease.
RA differentiation enhances dopaminergic features, changes redox parameters, and increases dopamine transporter dependency in 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells
Fernanda M Lopes, Fabio Klamt
Added on: 09-03-2021
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