Dataset Information
Modeling the mature CNS: A predictive screening platform for neurodegenerative disease drug discovery.
Ontology highlight
ABSTRACT: Background
Mature primary neuronal cultures are an important model of the nervous system, but limited scalability has been a major challenge in their use for drug discovery of neurodegenerative diseases. This work describes a method for improving scalability through the use of larger format microtiter plates while preserving culture quality.New method
Here we describe a method and quality control procedures for growing embryonic day 18 rat hippocampal/cortical neuronal cultures in 384-well microtiter plates for three weeks in vitro.Results
We use these cultures in two assays measuring intracellular lipid vesicle trafficking and synapse density for routine screening of small molecule libraries. Together this culture system and screening platform have successfully identified therapeutics capable of improving cognitive function in transgenic models of Alzheimer's disease that have advanced to clinical trials, validating their translational applicability.Comparison with existing methods
Our method enables the growth of healthy, mature neurons in larger format microtiter plates than in traditional primary neuronal culturing protocols, making it ideal for drug screening and mechanism of action studies.Conclusion
The predictive capacity of this culture system and screening platform provides a method for rapidly identifying novel disease-modifying neurodegenerative therapeutics.
SUBMITTER: LaBarbera KM
PROVIDER: S-EPMC8217273 | biostudies-literature | 2021 Jul
REPOSITORIES: biostudies-literature
Publications
Modeling the mature CNS: A predictive screening platform for neurodegenerative disease drug discovery.
Journal of neuroscience methods 20210406
<h4>Background</h4>Mature primary neuronal cultures are an important model of the nervous system, but limited scalability has been a major challenge in their use for drug discovery of neurodegenerative diseases. This work describes a method for improving scalability through the use of larger format microtiter plates while preserving culture quality.<h4>New method</h4>Here we describe a method and quality control procedures for growing embryonic day 18 rat hippocampal/cortical neuronal cultures i ...[more]