Embryonic BPF exposure induces neurodevelopmental and neurobehavioral toxicity by affecting neural stem cell proliferation in Drosophila

Abstract

BPF is a ubiquitous environmental chemical that has been shown to affect neurodevelopmental toxicity from animals to humans. Whether BPF exposure affects neural stem cell proliferation and differentiation is unknown. Here, we utilized a method of permeabilization of Drosophila embryos to analyze the effects of exposure to 0.5 mM, 1 mM, and 2 mM BPF on the proliferation and differentiation of neural stem cells. Our results showed that BPF exposure reduced the number of neuroblasts and intermediate neural progenitors during the embryonic stage, which caused the neuron/glial cell ratio to be out of balance, with a decrease in the number of neurons and an increase in the number of glial cells. BPF exposure caused neurotoxicity by reducing the activities of the antioxidant enzymes CAT and SOD, the downregulation of the transcriptional levels of oxidative stress-related genes, which triggered oxidative damage. As a result, embryonic BPF exposure affected the development of the neuromuscular junctions (NMJs) by reducing the number of axon branches and synaptic buttons, decreasing the number of peristaltic contractions, and reducing larval locomotion. In conclusion, our results demonstrate that embryonic BPF exposure disrupts neural stem cell proliferation, causing neurodevelopmental toxicity and abnormal larval behavior.