Transcriptome analysis of zebrafish exposed to neomycin and/or tacrine

Aminoglycosides remain in current use because of the benefits, including the broad-spectrum, inexpensiveness to produce, and a relatively small incidence of allergic reactions. However, aminoglycosides may induce irreversible hearing loss. Recently, tacrine, an acetylcholineesterase inhibitor originally developed to treat Alzheimer’s disease, was found to be protective to neomycin-induced hair cell damage in zebrafish and mouse. However, the protection mechanism remain to be largely unknown. In this study, we revealed that tacrine significantly suppressed the expression of tnf mRNA and ROS production induced by neomycin. Reduction of tnf expression by the antisense morpholino or transcription activator-like effectors nuclease significantly suppressed the hair cell damage but not ROS production induced by neomycin. In zebrafish treated with an antagonist of NMDA receptor MK-801 or a mitochondrial ROS inhibitor acetyl-L-carnitine, ROS production, tnf expression, and hair cell damage induced by neomycin were also significantly reduced. These levels of suppression were not significantly different from those of co-treatment of tacrine and MK-801 or acetyl-L-carnitine. These findings suggest that activation of NMDA receptor followed by ROS production and subsequent tnf expression are involved in neomycin-induced hair cell damage and that tacrine ameliorate neomycin-induced hair cell damage through inhibition of the signaling pathway. Gene expression regulated by neomycin and/or tacrine in zebrafish at 5 dpf was measured. Three independent experiments were performed for each group.