Abstract
Spiral ganglion neurons (SGNs) can be injured by a wide variety of insults. However, there still is a lack of degeneration models to specifically damage the SGNs without disturbing other types of cells in the inner ear. This study aims to generate an SGN-specific damage model using the Cre-LoxP transgenic mouse strains. The Cre-inducible diphtheria toxin receptor (iDTR+/+) knock-in mouse strain was crossed with a mouse strain with Cre activity specific to neurons (NeflCreER/CreER). Expression of the Cre-recombinase activity was evaluated using the reporter mouse strain Ai9 at pre-hearing, hearing onset, and post-hearing stages. Accordingly, heterozygous NeflCreER/+;iDTR+/– mice were treated with tamoxifen on postnatal days 1–5 (P1–5), followed by diphtheria toxin (DT) or vehicle injection on P7, P14, and P21 to evaluate the SGN loss. Robust tamoxifen-induced Cre-mediated Ai9 tdTomato fluorescence was observed in the SGN area of heterozygous NeflCreER/+;Ai9+/– mice treated with tamoxifen, whereas vehicle-treated heterozygote mice did not show tdTomato fluorescence. Compared to vehicle-treated NeflCreER/+;iDTR+/– mice, DT-treated NeflCreER/+;iDTR+/– mice showed significant auditory brainstem response (ABR) threshold shifts and SGN cell loss. Hair cell count and functional study did not show significant changes. These results demonstrate that the NeflCreER/CreER mouse strain exhibits inducible SGN-specific Cre activity in the inner ear, which may serve as a valuable SGN damage model for regeneration research of the inner ear.
Highlights
In the auditory system, spiral ganglion neurons (SGNs) are bipolar neurons that transfer auditory signals from auditory hair cells to the cochlear nucleus in the brainstem (Echteler, 1992; Nayagam et al, 2011)
Robust tdTomato fluorescence was observed in SGNs from P14 to postnatal day 28 (P28) in tamoxifentreated NeflCreER/+;Ai9+/− offspring, which overlapped with the neurofilament light chain (Nefl) immunofluorescence (Figures 2B–D)
It was found that NeflCreER/CreER mice exhibited Cre activity during the postnatal period from P1 to P28
Summary
Spiral ganglion neurons (SGNs) are bipolar neurons that transfer auditory signals from auditory hair cells to the cochlear nucleus in the brainstem (Echteler, 1992; Nayagam et al, 2011). Degeneration of SGNs usually causes irreversible sensorineural hearing loss, in which the auditory signals perceived by hair cells are not able to transfer to the cochlear nucleus. It is essential to establish an SGN damage model to understand the degeneration of SGNs. It is essential to establish an SGN damage model to understand the degeneration of SGNs This would provide fundamental knowledge to guide the prevention of SGN damage and the regeneration of SGNs to conduct auditory signals from the inner ear to the brainstem. Knowledge on the SGN degeneration model is very limited
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