New NTP assay for chemicals that affect neurological development
Researchers in the National Toxicology Program (NTP) led a collaborative team that, for the first time, screened 80 compounds with a high-throughput, high content assay using human neurons derived from induced pluripotent stem cells (iPSC). The screened compounds ranged from those associated with developmental neurotoxicity and neurotoxicity, to those with unknown potential, such as polycyclic aromatic hydrocarbons and flame retardants.
The results suggest the screen may narrow down the number of compounds that would undergo more comprehensive in vivo testing. Since previous assays were only able to screen small numbers of neurotoxic compounds, the iPSC studies represent an advance in developing reliable tools to identify environmental chemicals that could affect neurological development.
The scientists treated neurons for 72 hours in 384-well plates, using six different concentrations of each compound. They evaluated compound-specific effects on neurite growth by quantifying total outgrowth, branches, and processes. Simultaneously, they quantified cell viability, as a marker of nonspecific cell toxicity. Among the 80 compounds tested, 38 decreased neurite outgrowth or cell viability, with 16 specifically inhibiting neurite outgrowth. Twelve of the 16 compounds were associated with developmental neurotoxicity or neurotoxicity. Three were polycyclic aromatic hydrocarbons, and one was a flame retardant. Independent repeat studies of these 16 compounds verified six compounds that specifically inhibited neurite outgrowth more than cell viability. (RA)
Citation: Ryan KR, Sirenko O, Parham F, Hsieh JH, Cromwell EF, Tice RR, Behl M. 2016. Neurite outgrowth in human induced pluripotent stem cell-derived neurons as a high-throughput screen for developmental neurotoxicity or neurotoxicity. Neurotoxicology 53:271-281.