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bioRxiv · 10.1101/2024.02.21.581500

Spiral ganglion neuron degeneration in deafened rats involves innate and adaptive immune responses not requiring complement

Gansemer, B. M.·Rahman, M. T.·Zhang, Z.·Green, S. H.
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Abstract

Spiral ganglion neurons (SGNs) transmit auditory information from cochlear hair cells to the brain. SGNs are thus not only important for normal hearing, but also for effective functioning of cochlear implants, which stimulate SGNs when hair cells are missing. SGNs slowly degenerate following aminoglycoside-induced hair cell loss, a process thought to involve an immune response. However, the specific immune response pathways involved remain unknown. We used RNAseq to gain a deeper understanding immune-related and other transcriptomic changes that occur in the rat spiral ganglion after kanamycin-induced deafening. Among the immune and inflammatory genes that were selectively upregulated in deafened spiral ganglia, the complement cascade genes were prominent. We then assessed SGN survival, as well as immune cell infiltration and activation, in the spiral ganglia of rats with a CRISPR-Cas9-mediated knockout of complement component 3 (C3). Similar to previous findings in our lab and other deafened rodent models, we observed infiltration of macrophages and increased expression of CD68, a marker of phagocytic activity and cell activation, in the deafened ganglia. Moreover, we found that the immune response also includes MHCII+ macrophages and CD45+ and lymphocytes, indicative of an adaptive response. However, C3 knockout did affect SGN survival or macrophage infiltration/activation, indicating that complement activation does not play a role in SGN death after deafening. Together, these data suggest that both innate and adaptive immune responses are activated in the deafened spiral ganglion, with the adaptive response directly contributing to cochlear neurodegeneration.

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Gansemer, B. M., Rahman, M. T., Zhang, Z., Green, S. H.. 2024-02-23. Spiral ganglion neuron degeneration in deafened rats involves innate and adaptive immune responses not requiring complement. https://doi.org/10.1101/2024.02.21.581500

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