Machine learning-assisted neurotoxicity prediction in human midbrain organoids.

Parkinsonism & Related Disorders
Anna S MonzelJens Christian Schwamborn

Abstract

Brain organoids are highly complex multi-cellular tissue proxies, which have recently risen as novel tools to study neurodegenerative diseases such as Parkinson's disease (PD). However, with increasing complexity of the system, usage of quantitative tools becomes challenging. The primary objective of this study was to develop a neurotoxin-induced PD organoid model and to assess the neurotoxic effect on dopaminergic neurons using microscopy-based phenotyping in a high-content fashion. We describe a pipeline for a machine learning-based analytical method, allowing for detailed image-based cell profiling and toxicity prediction in brain organoids treated with the neurotoxic compound 6-hydroxydopamine (6-OHDA). We quantified features such as dopaminergic neuron count and neuronal complexity and built a machine learning classifier with the data to optimize data processing strategies and to discriminate between different treatment conditions. We validated the approach with high content imaging data from PD patient derived midbrain organoids. The here described model is a valuable tool for advanced in vitro PD modeling and to test putative neurotoxic compounds.

References

Oct 1, 1975·Journal of Neurochemistry·G Jonsson, C Sachs
Dec 1, 1968·European Journal of Pharmacology·U Ungerstedt
Jan 8, 2016·Parkinsonism & Related Disorders·Vanesa BellouJohn P A Ioannidis
Apr 19, 2017·Stem Cell Reports·Anna S MonzelJens C Schwamborn
Jun 26, 2018·Frontiers in Synaptic Neuroscience·Hansen Wang
Apr 10, 2019·NPJ Parkinson's Disease·Lisa M SmitsJens C Schwamborn

❮ Previous
Next ❯

Citations

Oct 1, 2020·International Journal of Molecular Sciences·Georgia KouroupiRebecca Matsas
Nov 4, 2020·Journal of Applied Toxicology : JAT·Anshul Srivastava, Joseph P Hanig
Apr 4, 2021·International Journal of Molecular Sciences·Gianluca CostamagnaStefania Corti
May 1, 2021·International Journal of Molecular Sciences·Katrina AlbertŠárka Lehtonen
Jun 29, 2021·Developmental Biology·Brian GuyRobert J Johnston
Jul 28, 2021·Methods : a Companion to Methods in Enzymology·Nguyen-Vi MohamedThomas M Durcan
Sep 24, 2021·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·Yuanyuan ZhengLijun Wu
Dec 11, 2021·Emerging Topics in Life Sciences·Loukia G Karacosta

❮ Previous
Next ❯

Related Concepts

Related Feeds

3D Cellular Models of Brain and Neurodegeneration

Brain organoids are three-dimensional in vitro cellular models of the brain that can recapitulate many processes such as the neurodevelopment. In addition, these organoids can be combined with other cell types, such as neurons and astrocytes to study their interactions in assembloids. Disease processes can also be modeled by induced pluripotent stem cell-derived organoids and assembloids from patients with neurodegenerative disorders. Discover the latest research on the models here.

Related Papers

BioRxiv : the Preprint Server for Biology
Anna S MonzelJens Christian Schwamborn
Frontiers in Cell and Developmental Biology
Lisa M Smits, Jens Christian Schwamborn
Nature Methods
Katherine Ellen Foley
© 2022 Meta ULC. All rights reserved