Insights into the mechanism of histamine synthesis and recycling disruption induced by exposure to CdO NPs in the fruit fly (Drosophila melanogaster).

Abstract

Exposure to a sublethal concentration of CdO nanoparticles impairs the vision of the fruit fly (Drosophila melanogaster) by disrupting histamine (HA) synthesis and recycling mechanisms. To gain more insights, we measured HA titer using HPLC in CdO NP-treated vs. non-treated adults in the current study and found that CdO NPs caused an increase in the level of HA in the head and the decapitated body. We asked whether HA accumulation (increase) is a response of photoreceptors or CNS histaminergic neurons, and whether there is any difference in the expression levels of HA recycling and transport encoding genes (Lovit, CarT, Ebony, Tan, BalaT) between the adult fly head and decapitated body that could explain this HA accumulation. We used GAL4/UAS system tool with three GAL4 drivers: ubiquitous tubP-GAL4, nervous system driver (elav Gal4), and compound eye drivers (sev Gal4 and GMR Gal4) to silence HA synthesis in site specific manner followed by detecting the expression level of genes involved in HA recycling and transport in both the heads and the decapitated bodies of CdO treated and non-treated flies. We found an increase in Lovit expression in the heads of treated adults, which is responsible for HA loading into synaptic vesicles and release from photoreceptors, as well as a decrease in catalytic enzymes involved in HA recycling, which leads to HA accumulation without increasing the real signal. To conclude, both photoreceptors and CNS histaminergic neurons are responsible for the increase in HA in CdO NP-treated flies, but through different mechanisms. Our results provide more insights on the underlying molecular mechanism of vision impairment because of nano-sized cadmium particles exposure.