Botulinum neurotoxins A, B, C, E, and F preferentially enter cultured human motor neurons compared to other cultured human neuronal populations.

Human-induced pluripotent stem cell (hiPSC)-derived neurons can be exquisitely sensitive to botulinum neurotoxins (BoNTs), exceeding sensitivity of the traditionally used mouse bioassay. In this report, four defined hiPSC-derived neuronal populations including primarily GABAergic, glutamatergic, dopaminergic, and motor neurons were examined for BoNT/A, B, C, D, E, and F sensitivity. The data indicate that sensitivity varies markedly for the BoNTs tested. Motor neurons are significantly more sensitive than other neuron types for all BoNTs except BoNT/D. Examination of SNARE protein levels and BoNT-specific cell surface protein receptors reveals few differences between the cell types except greater expression levels of the receptor protein SV2C and synapsin-IIa in motor neurons. This indicates that differential toxicity of BoNTs for motor neurons compared to other neuronal cell types involves multiple mechanisms.