Electrical Stimulation Reduces Apoptotic Signaling in SGNs

Abstract

Objective: To establish the intracellular consequences of electrical stimulation (ES) to spiral ganglion neurons (SGNs) after deafferentation. SGNs die as a result of loss of hair cells, their sole afferent input. Some histologic animal studies of chronic ES after deafening show that ES alone may improve SGN survival. Here we use a rat model to determine the effect of both low and high pulse rate ES on activation of the pro-apoptotic transcription factor Jun in deafferented SGNs in vivo. Methods: A single electrode was implanted through the round window of kanamycin-deafened rats at either postnatal day 32 (P32) or P60 for 4 hours of ES (monopolar, biphasic pulses, amplitude twice eABR threshold) at either 100 or 5000 Hz. Jun phosphorylation, a proapoptotic signaling event known to occur in apoptotic SGNs after deafening, was assayed by immunofluorescence to quantitatively assess the effect of ES on proapoptotic signaling. Results: Jun phosphorylation was reliably suppressed by 100 Hz ES in deafened cochleae of P32 rats ( P = .045) but this effect was less robust when 5000 Hz ES was used. This effect was most significant in the cochlear turn just apical to the stimulating electrode and was not significant in P60 rats. Conclusion: Suppression of phospho-Jun occurs in deafferented SGNs after only 4 hours of ES, consistent with the hypothesis that ES provides trophic support to SGNs after deafferentation. Stimulation frequency may be consequential: 100 Hz ES was significantly more effective than 5000 Hz ES in suppressing phospho-Jun.