Wnt signaling activates TIGAR and protects against cisplatin-induced spiral ganglion neuron damage in the mouse cochlea

Aims: Cisplatin can damage spiral ganglion neurons (SGNs) and cause sensorineural hearing loss. Wnt activation protects against neomycin-induced hair cell damage in the mouse cochlea, but the role of Wnt signaling in protecting SGNs from cisplatin treatment has not yet been elucidated. This study was designed to investigate the neuroprotective effects of Wnt signaling against cisplatin-induced SGN damage. Results: Firstly, we found that Wnt signaling was activated in SGNs after cisplatin treatment. Next, we discovered that overexpression of Wnt signaling in SGNs reduced cisplatin-induced SGN loss by inhibiting Caspase-associated apoptosis, thus preventing the loss of SGN function after cisplatin treatment. In contrast, inhibition of Wnt signaling increased apoptosis, made SGNs more vulnerable to cisplatin treatment, and exacerbated hearing loss. TP53-induced glycolysis and apoptosis regulator (TIGAR), which scavenges intracellular reactive oxygen species (ROS), was upregulated in SGNs in response to cispl...