■ OBJECTIVES: Hair cells and spiral ganglion cells appear to be more vulnerable to toxins at the base of the cochlea than at the apex. For example, aminoglycosides and cisplatin produce hearing loss in a high to low frequency gradient corresponding to sensorineural damage in a base-to-apex gradient of the cochlea. Age-related hearing loss also begins with high frequencies represented at the base of the cochlea. Sha et al. (Hearing Res., 155, 2001, 1-8) reported that the differential vulnerability of basal and apical hair cells coincided with a significantly lower level of antioxidant glutathione in basal outer hair cells. However, there are no previous reports of a similar gradient in reactive oxygen species (ROS) mechanisms in the spiral ganglion. This study examined expression of the mitochondrial manganese superoxide dismutase (Mn SOD2) in the cochlea.

■ METHODS: Immunohistochemical methods were used to identify the distribution of Mn SOD2 in paraffin embedded sections of paraformaldehyde fixed formic acid decalcified temporal bones from  mice, rats, and macaques; and special archival celloidin-embedded human temporal bone sections. Binding sites of primary rabbit polyclonal antibodies to Mn SOD2 (Abcam Inc., ab13534) were visualized with standard ABC methods and a diaminobenzidine chromogen.

■ RESULTS: Both the proportion of Mn SOD2 immunopositive spiral ganglion cells and the intensity of immunoreactivity were greater in the apical turn than in the basal turn in all species. For example, there is a three-fold greater proportion of Mn SOD2 immunopositive spiral ganglion cells in the apical versus basal turn.

■ CONCLUSIONS: Mn SOD2 activation reduces mitochondrial ROS production by contributing to activation of mitochondrial uncoupling proteins. The data indicate that spiral ganglion cellular responses to ROS exposure vary along the cochlear spiral, with a lower response capacity in the basal turn. These results raise the broader question of how the regional distribution of multiple ROS metabolic pathways may contribute to age-related and toxin-induced patterns of hearing loss. Furthermore, the similar patterns of spiral ganglion Mn SOD2 distribution suggest if there is an ubiquitous protective mechanism shared across all mammalian species in response to ROS.