FoxO signaling pathway stimulation by Bacillus smithii XY1 contributes to alleviating copper-induced neurotoxicity.

ABSTRACT

Increasingly copper pollution in the environment exacerbates the risk of neurodegenerative diseases. It is necessary to look for effective targets and safe methods for protecting from copper-induced neurotoxicity. Here we firstly explored the impact of copper-exposure on expression profiles in zebrafish. Copper reduced embryo hatching, increased mortality and caused embryonic developmental abnormalities and behavioral dysfunction in juveniles. Transcriptomic analysis revealed that differential genes related to neuron were highly associated with oxidative stress especially enriched to FoxO pathway. Through further validation in Caenorhabditis elegans, copper resulted in nematode neurodegenerative movement disorders and neuronal damage, along with increased levels of reactive oxygen species (ROS) as well as decreased expressions of antioxidant-related enzymes and downstream genes which was also involved in FoxO signaling pathway. Bacillus smithii XY1, a novel strain with an excellent antioxidative activity, showed a great alleviative effect on copper-induced neurotoxicity that was related to FoxO stimulation, being a potential candidate for copper pollution management. Overall, these results suggested that FoxO pathway activation can regard as a strategy for mitigating neurotoxicity caused by copper and B. smithii XY1 with excellent tolerance and outstanding antioxidation specially targeted for FoxO has a promising application in controlling copper contamination.