Taurine enhances mouse cochlear neural stem cell transplantation via the cochlear lateral wall for replacement of degenerated spiral ganglion neurons via sonic hedgehog signaling pathway

摘要

The aim of this paper is to investigate the potential beneficial effects of taurine in cochlear neural stem cell (NSC) transplantation and elucidate the underlying molecular mechanism. The NSC cells were isolated from neonatal Balb/c mice and an auditory neuropathy gerbil model was established by microinjection of ouabain. The spiral ganglion neurons (SGN) were characterized with immunofluorescence stained with Tuj1 antibody. Cell proliferation was determined by BrdU incorporation assay and the morphologic index was measured under the light microscope. The relative protein level was determined by immunoblotting. The hearing of the animal model was scored by click- and tone burst-evoked auditory brainstem response (ABR). Here we consolidated our previous finding that taurine stimulated SGN density and the proliferation index, which were completely abolished by Shh inhibitor, cyclopamine. Transplantation of cochlear NSCs combined with taurine significantly improved ouabain-induced auditory neuropathy in gerbils. In addition, cyclopamine antagonized taurine's effect on glutamatergic and GABAergic neuron population via suppression of VGLUT1 and GAT1 expression. Mechanistically, taurine evidently activated the Sonic HedgeHog pathway and upregulated Shh, Ptc-1, Smo and Gli-1 proteins, which were specifically blockaded by cyclopamine. Here, for the first time demonstrated we that co-administration with taurine significantly improved NSC transplantation and the Shh pathway was identified in this beneficial effect.