Non Animal Testing Database

Brain model to study chemical-induced dopaminergic neuronal toxicity

Johns Hopkins University, Baltimore, USA
In the context of Parkinson's disease (PD), the sensitivity of dopaminergic neurons in the substantia nigra pars compacta to oxidative stress is considered a key factor of PD pathogenesis. Here the effect of different oxidative stress-inducing compounds (6-OHDA, MPTP or MPP+) on the population of dopaminergic neurons was studied in an iPSC-derived human brain 3D model (aka BrainSpheres). Treatment with 6-OHDA, MPTP or MPP+ at 4 weeks of differentiation disrupted the dopaminergic neuronal phenotype in BrainSpheres. 6-OHDA increased the production of reactive oxygen species and decreased mitochondrial function most efficiently. It further induced the greatest changes in gene expression and metabolites related to oxidative stress and mitochondrial dysfunction. Co-culturing BrainSpheres with an endothelial barrier using a transwell system allowed the assessment of differential penetration capacities of the tested compounds and the damage they caused in the dopaminergic neurons within the BrainSpheres. In conclusion, treatment with compounds known to induce PD-like phenotypes in vivo caused molecular deficits and loss of dopaminergic neurons in the BrainSphere model. This approach, therefore, recapitulates neurodegenerative processes in PD and could be relevant as a tool for drug discovery.
Human iPSC 3D brain model as a tool to study chemical-induced dopaminergic neuronal toxicity
David Pamies
Added on: 05-12-2022
Back to Top
English German

Warning: Internet Explorer

The IE from MS no longer understands current scripting languages, the latest main version (version 11) is from 2013 and has not been further developed since 2015.

Our recommendation: Use only the latest versions of modern browsers, for example Google Chrome, Mozilla Firefox or Microsofrt Edge, because only this guarantees you sufficient protection against infections and the correct display of websites!