Reciprocal signaling between spiral ganglion neurons and Schwann cells involves neuregulin and neurotrophins.

To investigate the role of neuron-glial cell interactions in the auditory nerve, we asked whether spiral ganglion neurons (SGNs) express neuregulin and whether neuregulin regulates proliferation and/or neurotrophin expression in spiral ganglion Schwann cells (SGSCs). Using immunocytochemistry, we found that type I and type II SGNs express neuregulin in vivo and in vitro. Cultured SGSCs express the neuregulin receptors ErbB2 and ErbB3, but not ErbB4. Neuregulin activates ErbB2 and ErbB3 in cultured SGSCs, evidenced by increased tyrosine phosphorylation of the receptors following neuregulin treatment. Neuregulin treatment increased the proliferation rate of cultured SGSCs by 2.5-fold. Fibroblast growth factor-2 (FGF-2) and transforming growth factor beta (TGF-beta) also increased SGSC proliferation. The mitogenic effect of neuregulin and FGF-2 was blocked by inhibition of mitogen-activated protein kinase signaling but not by inhibition of phosphatidylinositol-3'-OH kinase. Using RT-PCR, we found that cultured SGSCs express neurotrophins, including brain-derived neurotrophic factor and neurotrophin-3 (NT-3), raising the possibility that SGSCs contribute to the trophic support of SGNs. Treatment with neither neuregulin nor TGF-beta increased neurotrophin expression in cultured SGSCs, as had been observed in developing sympathetic ganglia, but appeared to negatively regulate NT-3 expression. Thus, neuregulin and neurotrophins may mediate reciprocal neuron-glial interactions in the auditory nerve.