The expression pattern and inhibitory influence of Tenascin-C on the growth of spiral ganglion neurons suggest a regulatory role as boundary formation molecule in the postnatal mouse inner ear

Abstract

Sensorineural hearing loss, as a consequence of acoustic trauma, aging, genetic defects or ototoxic drugs, is highly associated with irreversible damage of cochlear hair cells (HCs) and secondary degeneration of spiral ganglion (SG) cells. Cochlear implants (CIs), which bypass the lost HC function by direct electrical stimulation of the remaining auditory neurons, offer an effective therapy option. Several studies imply that components of the extracellular matrix (ECM) have a great impact on the adhesion and growth of spiral ganglion neurons (SGNs) during development. Based on these findings, ECM proteins might act as bioactive CI substrates to optimize the electrode-nerve interface and to improve efficacy of these implants. In the present study, we focused on the ECM glycoproteins Tenascin-C (TN-C), Laminin (LN), and Fibronectin (FN), which show a prominent expression along the growth route of SGNs and the niche around HCs during murine postnatal development in vivo. We compared their influence on adhesion, neurite length, and neurite number of SGNs in vitro. Moreover, we studied the expression of the chondroitin sulfate proteoglycan (CSPG) dermatan sulfate-dependent proteoglycan-1 (DSD-1-PG), an interaction partner of TN-C. In sum, our in vitro data suggest that TN-C acts as an anti-adhesive and inhibitory factor for the growth of SGNs. The DSD-1 carbohydrate epitope is specifically localized to HC stereocilia and SG fibers. Interestingly, TN-C and the DSD-1-PG exhibit a mutually exclusive expression pattern, with the exception of a very restricted region beneath the habenula perforata, where SG neurites grow through the basilar membrane (BM) toward the HCs. The complementary expression of TN-C, LN, FN, and the DSD-1 epitope suggests that TN-C may act as an important boundary formation molecule in the developing postnatal mouse inner ear, which makes it a promising candidate to regulate neurite outgrowth in the light of CIs.

Keywords: DSD-1-PG; Tenascin-C; cochlear implant; extracellular matrix; neurite growth; spiral ganglion neurons.