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

• Published in: Hearing research Vol. 161; no. 1; pp. 87 - 98
• Main Authors: Hansen, Marlan R, Vijapurkar, Ulka, Koland, John G, Green, Steven H
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.11.2001; Elsevier
• Subjects: Animals; Biological and medical sciences; Cell Division - drug effects; Cell proliferation; Cell survival; Cells, Cultured; Cochlea - metabolism; Ear and associated structures. Auditory pathways and centers. Hearing. Vocal organ. Phonation. Sound production. Echolocation; Fundamental and applied biological sciences. Psychology; Mitogen-Activated Protein Kinases - physiology; Nerve Growth Factors - physiology; Neuregulin; Neuregulin-1 - pharmacology; Neuregulin-1 - physiology; Neurons - cytology; Neurons - physiology; Neurotrophin; Neurotrophin 3 - metabolism; Rats; Receptor, ErbB-2 - metabolism; Receptor, ErbB-3 - metabolism; Schwann cell; Schwann Cells - physiology; Signal Transduction - physiology; Spiral Ganglion - cytology; Spiral Ganglion - physiology; Spiral ganglion neuron; Vertebrates: nervous system and sense organs; Cell proliferation; Neurotrophin; PI3-K, phosphatidylinositol-3′-OH kinase; GFAP, glial fibrillary acidic protein; EGF, epidermal growth factor; BrdU, 5-bromodeoxyuridine; TGF-β, transforming growth factor β; NGF, nerve growth factor; SGN, spiral ganglion neuron; SDS, sodium dodecyl sulfate; TRITC, tetramethylrhodamine isothiocyanate; PBS, phosphate-buffered saline; Schwann cell; NF200, neurofilament 200 kDa protein; Neuregulin; RT, reverse transcriptase; IGF, insulin-like growth factor; SG, spiral ganglion; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; Spiral ganglion neuron; Cell survival; DMEM, Dulbecco’s modified essential medium; FITC, fluorescein isothiocyanate; FGF-2, fibroblast growth factor-2; NT-3, neurotrophin-3; BDNF, brain-derived neurotrophic factor; PCR, polymerase chain reaction; SGSC, spiral ganglion Schwann cell; NT-4, neurotrophin-4; NRG, neuregulin; PDGF, platelet-derived growth factor; MAPK, mitogen-activated protein kinase; FCS, fetal calf serum; Spiral ganglion; Rat; Transforming growth factor β; Neuroglia; Rodentia; Cell cell interaction; Basic fibroblast growth factor; Gene expression; Auditory nerve; Inner ear; Organ of hearing; Ganglion neuron; Signal transduction; Vertebrata; Growth factor receptor; Mammalia; Cochlea
• ISSN: 0378-5955; 1878-5891
• DOI: 10.1016/S0378-5955(01)00360-4

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 β (TGF-β) 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-β 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.