2-Bromopalmitate impairs neural stem/progenitor cell proliferation, promotes cell apoptosis and induces malformation in zebrafish embryonic brain

Abstract

2-Bromopalmitate (2BP) is a widely used palmitoylation inhibitor. Besides, it has been reported that 2BP can inhibit T-cell activation, making it a potential immunosuppressor for the treatment of autoimmune diseases. Although the important roles of palmitoylation in a neural system have been noted during the past decades, the effect of 2BP on neural development is still not very clear. In this study, we demonstrated that 25 μM-100 μM 2BP exposure caused apparent neural malformation in the presumptive brains of zebrafish embryos at 14 hpf. Further studies implied that the mRNA quantities and distributions of neural stem/progenitor cell (NSPC) markers (neurog1, sox2, and sox3) in the affected regions of 50 μM 2BP treated embryos significantly decreased. In addition, we found that 2BP impaired the NSPC proliferation at 10 hpf and 14 hpf as well as promoted cell apoptosis at 14 hpf, consistent with which the interference with FGF/ERK signaling pathway was also detected. For the first time, this study provided information about the toxicity and teratogenicity of 2BP for neural development in vivo.

Keywords: 2-Bromopalmitate; FGF signaling pathway; Neural development; Neural stem/progenitor cells; Palmitoylation; Zebrafish.