Intracochlear Electrical Stimulation Suppresses Apoptotic Signaling in Rat Spiral Ganglion Neurons after Deafening in Vivo

Abstract

Objective To establish the intracellular consequences of electrical stimulation to spiral ganglion neurons after deafferentation. Here we use a rat model to determine the effect of both low and high pulse rate acute electrical stimulation on activation of the proapoptotic transcription factor Jun in deafferented spiral ganglion neurons in vivo. Study design Experimental animal study. Setting Hearing research laboratories of the University of Iowa Departments of Biology and Otolaryngology Methods A single electrode was implanted through the round window of kanamycin-deafened rats at either postnatal day 32 (P32, n=24) or P60 (n=22) for four hours of stimulation (monopolar, biphasic pulses, amplitude twice eABR threshold) at either 100 or 5000 Hz. Jun phosphorylation was assayed by immunofluorescence to quantitatively assess the effect of electrical stimulation on proapoptotic signaling. Results Jun phosphorylation was reliably suppressed by 100 Hz stimuli in deafened cochleae of P32 but not P60 rats. This effect was not significant in the basal cochlear turns. Stimulation frequency may be consequential: 100 Hz was significantly more effective than was 5 kHz stimulation in suppressing phospho-Jun. Conclusions Suppression of Jun phosphorylation occurs in deafferented spiral ganglion neurons after only four hours of electrical stimulation. This finding is consistent with the hypothesis that electrical stimulation can decrease spiral ganglion neuron death after deafferentation.

Kanamycin Damages Early Postnatal, but Not Adult Spiral Ganglion Neurons

“…Several weeks or months after aminoglycoside-induced hair cell loss has occurred in vivo , the spiral ganglion neurons (SGN) begin to die off (Kopelovich et al, 2013, McFadden et al, 2004, Yu et al, 2014). SGN degeneration continues over weeks and months (Xu et al, 1993) further exacerbating the cochlear pathology.…”

Neurons Self-Organize Around Salivary Epithelial Cells in Novel Co-Culture Model

“…( Figure 2C and 2G ) show cell nuclei, while ( Figure 3D and 3H ) show an overlay image. β-3-tubulin is a microtubule protein from the β-tubulin family expressed exclusively in central and peripheral neurons [ 22 ] , and has been used as a neuronal marker in a variety of in vitro and in vivo studies [ 23 , 24 ] . The observed pattern of β-3-tubulin staining indicates a branching neuronal morphology typical of the salivary gland [ 25 ] , which can explain the non-uniformity of β-3-tubulin staining as innervation of salivary structures by progressively fewer numbers of neurons as the salivary structures get smaller.…”

Cochlear-Bioelectrode: Auditory response to cochlear implant can be improved by stem cell delivery into inner ear in a pig model

“…In animals with extensive neural pathology, EABR thresholds are elevated with response amplitudes greatly reduced. With hearing loss, SGN may gradually degenerate following cochlear hair cell loss, leaving fewer neurons available for stimulation, which compromises the e cacy of cochlear implants (33)(34)(35). Compared to the normal cochlea, the cochlea of congenitally deaf Rongchang pigs showed far fewer SGNs and severely reduced EABR amplitudes after the cochlear implants.…”