Survival of Adult Spiral Ganglion Neurons Requires erbB Receptor Signaling in the Inner Ear

Abstract

Degeneration of cochlear sensory neurons is an important cause of hearing loss, but the mechanisms that maintain the survival of adult cochlear sensory neurons are not clearly defined. We now provide evidence implicating the neuregulin (NRG)-erbB receptor signaling pathway in this process. We found that NRG1 is expressed by spiral ganglion neurons (SGNs), whereas erbB2 and erbB3 are expressed by supporting cells of the organ of Corti, suggesting that these molecules mediate interactions between these cells. Transgenic mice in which erbB signaling in adult supporting cells is disrupted by expression of a dominant-negative erbB receptor show severe hearing loss and 80% postnatal loss of type-I SGNs without concomitant loss of the sensory cells that they contact. Quantitative RT-PCR analysis of neurotrophic factor expression shows a specific downregulation in expression of neurotrophin-3 (NT3) in the transgenic cochleas before the onset of neuronal death. Because NT3 is critical for survival of type I SGNs during development, these results suggest that it plays similar roles in the adult. Together, the data indicate that adult cochlear supporting cells provide critical trophic support to the neurons, that survival of postnatal cochlear sensory neurons depends on reciprocal interactions between neurons and supporting cells, and that these interactions are mediated by NRG and neurotrophins.

Supporting Cell Characteristics in Long-deafened Aged Mouse Ears

“…Hence, the persistence of the tunnel of Corti and maintained morphological differentiation of the SCs 1 year after drug treatment that were seen here in spite of marked HC loss and partial SC loss is unusual, but it is not unprecedented. For example, differentiated SCs can persist for 3-years post treatment in cats after a series of kanamycin injections in spite of total HC loss (Sugawara et al 2005). In one of the eight animals studied (Figs.…”

“…The resprouting processes were identified morphologically on the basis of their abnormal projections that are substantially different to the well-structured and uniform innervation patterns seen in the normal undamaged cochlea. Acetylcholinesterase immunohistochemistry (AChE) in noise-damaged chinchilla cochlea has shown that the regenerated fibers do not express AChE, suggesting they are not efferent and therefore most likely are afferent (Strominger et al 1995). The spiral ganglion cell and peripheral process survival may be dependent on trophic support provided by SCs remaining in the epithelium and erbB receptor signaling (Stankovic et al 2004).…”

Selective Inner Hair Cell Loss in Prematurity: A Temporal Bone Study of Infants from a Neonatal Intensive Care Unit

“…Although we saw no signs of neural loss in the present study, the longest postnatal survival in an ear with selective IHC loss was only 1 month (see Table 1). The continued presence of supporting cells in the IHC area ( Figure 1D-F) is important in this regard, given recent evidence that these supporting cells are a key source of the neurotrophins required for survival of spiral ganglion cells (Stankovic et al 2004;Sugawara et al 2005). If the supporting cellsupplied neurotrophins are sufficient to promote long-term neuronal survival in the absence of IHCs, patients with an AN associated with prematurity might benefit more from cochlear implants than those with AN arising from primary neural degeneration.…”

Ouabain-Induced Cochlear Nerve Degeneration: Synaptic Loss and Plasticity in a Mouse Model of Auditory Neuropathy

“…The cochlear frequency correlate of each half-turn visible in these mid-modiolar sections was determined as described previously (Stankovic et al, 2004). In each case, the total number of SGNs was counted in three mid-modiolar sections through Rosenthal's canal.…”