Department of Otolaryngology Head and Neck Surgery, University of Iowa, Iowa City, Iowa, USA.
Otolaryngol Head Neck Surg. 2013 Nov;149(5):745-52. doi: 10.1177/0194599813498702. Epub 2013 Aug 1.
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.
Experimental animal study.
Hearing research laboratories of the University of Iowa Departments of Biology and Otolaryngology.
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 4 hours of stimulation (monopolar, biphasic pulses, amplitude twice electrically evoked auditory brainstem response [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.
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.
Suppression of Jun phosphorylation occurs in deafferented spiral ganglion neurons after only 4 hours of electrical stimulation. This finding is consistent with the hypothesis that electrical stimulation can decrease spiral ganglion neuron death after deafferentation.
确定去传入后螺旋神经节神经元电刺激的细胞内后果。在这里,我们使用大鼠模型来确定低和高脉冲率急性电刺激对体内去传入螺旋神经节神经元凋亡转录因子 Jun 激活的影响。
实验动物研究。
爱荷华大学生物学和耳鼻喉科系的听力研究实验室。
在出生后第 32 天(P32,n = 24)或第 60 天(P60,n = 22)的卡那霉素耳聋大鼠的圆窗中植入单个电极,进行 4 小时的刺激(单极,双相脉冲,幅度为电诱发听脑干反应[eABR]阈值的两倍),频率为 100 Hz 或 5000 Hz。通过免疫荧光法测定 Jun 磷酸化,定量评估电刺激对促凋亡信号的影响。
在 P32 但不在 P60 耳聋耳蜗中,100 Hz 刺激可靠地抑制了 Jun 磷酸化。这种效应在基底耳蜗转中并不显著。刺激频率可能具有重要意义:100 Hz 比 5 kHz 刺激更有效地抑制磷酸化 Jun。
在去传入后仅 4 小时的电刺激后,去传入螺旋神经节神经元中就会发生 Jun 磷酸化的抑制。这一发现与电刺激可以减少去传入后螺旋神经节神经元死亡的假设一致。