R450 – Manganese Superoxide Dismutase in Spiral Ganglion Cells

Problem Manganese superoxide dismutase (Mn SOD2) is a key metabolic anti-oxidant enzyme of the superoxide dismutase family for detoxifying the free radical cascade inside the mitochondria of the cochlea via activation of downstream uncoupling proteins. Copper/zinc superoxide dismutase (Cu/Zn SOD1) is localized in the cytoplasm. This study examined whether the pattern of expression of these SODs in the cochlea is correlated with the differential cellular vulnerability found in basal versus apical turn of the cochlea. Methods Immunohistochemical methods were used to identify the distribution of Mn SOD2 and Cu/Zn SOD1 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. Results In mice, rats and macaques, both the proportion of Mn SOD2 immunopositive type 1 spiral ganglion cells and the intensity of immunoreactivity were elevated near the cochlear apex. Strongly stained Mn SOD2 type 1 spiral ganglion cells were also observed in archival human temporal bone sections. In contrast, the Cu/Zn SOD1 immunopositive type 1 spiral ganglion cells were distributed identically across cochlear turns in rats and macaques. Conclusion These findings suggest that spiral ganglion cellular responses to ROS exposure may vary along the cochlear spiral, with a lower response capacity in the basal turn. Significance Hair cells and spiral ganglion cells appear to be more vulnerable to ototoxins at the base of the cochlea than at the apex. Our data raises the general hypothesis that a lower Mn SOD2 anti-oxidative capacity at the cochlear base could contribute to the high frequency hearing loss seen in presbycusis and ototoxin-induced hearing loss. The conservative pattern of Mn SOD2 immunostaining across species further suggests that it may be a fundamental mechanism in ROS metabolism and signaling. Support PA Lions Hearing Research Foundation, American Otologic Society Research Fellowship.