Toxicity, recovery, and resilience in a 3D dopaminergic neuronal in vitro model exposed to rotenone.

ABSTRACT: To date, most in vitro toxicity testing has focused on acute effects of compounds at high concentrations. This testing strategy does not reflect real-life exposures, which might contribute to long-term disease outcome. We used a 3D-human dopaminergic in vitro LUHMES cell line model to determine whether effects of short-term rotenone exposure (100 nM, 24 h) are permanent or reversible. A decrease in complex I activity, ATP, mitochondrial diameter, and neurite outgrowth were observed acutely. After compound removal, complex I activity was still inhibited; however, ATP levels were increased, cells were electrically active and aggregates restored neurite outgrowth integrity and mitochondrial morphology. We identified significant transcriptomic changes after 24 h which were not present 7 days a

SUBMITTER: Harris G 

PROVIDER: S-EPMC6063347 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature