Effects of gentamicin on guinea pig vestibular ganglion function and on substance P and neuropeptide Y

Previous studies have demonstrated that following intratympanic gentamicin application in the guinea pigs, vestibular evoked myogenic potentials (VEMPs) were absent regardless of stimulation mode using either air-conducted sound (ACS) stimuli or galvanic vestibular stimulation (GVS). Ultrastructurally, both type I hair cells and their calyx terminals were distorted in the saccular macula. However, little is known about the toxic effects of gentamicin on the vestibular ganglion (VG). In this study, absent ACS- and GVS-VEMPs were noted in all the gentamicin-treated ears (100%), which were confirmed by the substantial loss of sensory hair cells in the saccular macula. Moreover, dramatic up-regulation of growth associated protein-43 (GAP-43) expression was detected in the ipsilateral VG neurons. The mean percentage of substance P-like immunoreactive (SP-LI) neurons in the treated VG (81.8 ± 1.9%) was significantly higher than that in the control VG (68.6 ± 3.3%). Conversely, the mean percentage of neuropeptide Y-like immunoreactive (NPY-LI) neurons in the treated VG (13.7 ± 3.8%) was dramatically lower than that in the control VG (49.0 ± 3.8%). Double labeling results shown 82% of SP-LI and 16% of NPY-LI neurons coexpressed with GAP-43, suggested that SP accumulating coincided with NPY decreasing in regenerating VG neurons after gentamicin treatment. Overall, the changes in SP and NPY expression in VG neurons after gentamicin treatment were like to those in the superior cervical ganglion following sympathectomy.

Research highlights▶ Gentamicin damages to saccular macula and vestibular afferents may result in absent ACS- and GVS-VEMPs in the gentamicin-treated ears. ▶ Gentamicin treatment may result in damage to the VG neurons to induce GAP-43 up-regulation. ▶ Gentamicin-induced SP increases because of decreased release in the VG neurons. ▶ Gentamicin-induced NPY decreases because of decreased in the VG neurons.