Developmental neurotoxicity evaluation: On the road to regulatory acceptance
August 28, 2019
10:00 - 11:00 AM EDT
Registration link: https://attendee.gotowebinar.com/register/1377474065309490957
Presenter: Prof. Ellen Fritsche
Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany
Testing for developmental neurotoxicity (DNT) of compounds for regulatory purposes, e.g. for screening and priorisation, by using an in vitro testing battery is currently under discussion at the OECD level. Within such a battery a variety of neurodevelopmental processes at different developmental stages needs consideration. We have been establishing a DNT high content assay based on time-matched fetal human and postnatal rodent as well as human induced pluripotent stem cell (hiPSC)-derived neural progenitor cells (NPCs), which proliferate in culture and - under differentiating conditions – migrate and differentiate into neurons and glia cells, i.e. radial glia, astrocytes and oligodendrocytes. In this so-called ‘Neurosphere Assay’ we analyzed multiple pathways for their functional implications in neurodevelopmental processes, amongst them oxidative stress, histone deacetylase inhibition or thyroid hormone disruption. For high content analyses of differentiated neurospheres, we developed the software ‘Omnisphero’ allowing simultaneous analyses of multiple neurodevelopmental endpoints like NPC migration, neuron and glia differentiation, neuronal morphology and neuronal migration. This set-up allows chemical testing in a medium throughput with the ‘Neurosphere Assay’ as part of a DNT testing battery, e.g. for industrial or regulatory usage.