Localization of Synucleins in the Mammalian Cochlea

Synucleins are widely expressed synaptic proteins within the central nervous system that have been implicated in such neurodegenerative disorders as Parkinson’s disease. In this study, an initial characterization of all three synucleins, α-, β-, and γ-synuclein, within the cochlea was undertaken. Reverse transcriptase-polymerase chain reaction (PCR) demonstrated all three synuclein mRNA species within microdissected cochlear tissue. Quantitative PCR suggests that β-synuclein is the most abundantly expressed form, followed by γ- and then α-synuclein. Western blot analysis similarly demonstrates all three synuclein proteins within microdissected cochlear tissue. Immunofluorescence localizes the three synucleins predominantly to the efferent neuronal system at the efferent outer hair cell synapse, with some additional localization within the efferent tunnel-crossing fibers (α- and γ-synuclein), spiral ganglion (β-synuclein), inner spiral bundle (γ-synuclein), and stria vascularis (α- > β-synuclein). Developmentally, γ-synuclein can be seen in the region of the outer hair cells by E19, while α- and β-synuclein do not clearly appear there until ~P10. Addi-tional studies in a null-mutant γ-synuclein mouse show no histological changes in the organ of Corti with normal hair cell and spiral ganglion cell counts, and normal ABR and DPOAE thresholds in wild-type vs mutant littermates. Together, these results localize synucleins to the efferent cholinergic neuronal auditory system, pointing to a role in normal auditory function, and raising the potential implications for their role in auditory neurodegenerative disorders. However, γ-synuclein alone is not required for the development and maintenance of normal hearing through P21. Whether overlapping roles of the other synucleins help compensate for the loss of γ-synuclein remains to be determined.