Murai Norihiko, Kirkegaard Mette, Järlebark Leif, Risling Mårten, Suneson Anders, Ulfendahl Mats
Department of Otolaryngology, Kyoto-Katsura Hospital, Kyoto, Japan.
J Neurotrauma. 2008 Jan;25(1):72-7. doi: 10.1089/neu.2007.0346.
Noise exposure is known to induce cell death signaling in the cochlea. Since c-Jun N-terminal kinase (JNK) signaling is known to induce both cell survival and apoptosis, the present study focused on early changes (within 24 h) after impulse noise exposure, inquiring whether cell death is always related to phosphorylation of JNK in the inner ear. Anesthetized adult albino rats were exposed to a single impulse noise exposure (194 kPa) and sacrificed 3 or 24 h later. Paraffin-embedded sections were examined for positive staining of phosphorylated JNK and the presence of cells with fragmented DNA (TUNEL staining). Positive TUNEL staining was observed at the spiral limbus and in the stria vascularis at 24 h following impulse noise exposure, but no correlation with JNK activation was found at these locations. In the hearing organ (organ of Corti) and in the lateral wall, TUNEL-reactive cells were observed at 24 h following trauma. This was preceded by p-JNK staining at 3 h, indicating JNK-activated cell death in these regions. Finally, p-JNK reactivity was observed in the spiral ganglion with no correlation to TUNEL staining within the time frame of this study. These results suggest that JNK activation following impulse noise exposure may not always be related to cell death, and conversely, some cells may die through JNK-independent signaling.
已知噪声暴露会在耳蜗中诱导细胞死亡信号。由于已知c-Jun氨基末端激酶（JNK）信号传导既能诱导细胞存活又能诱导细胞凋亡，因此本研究聚焦于脉冲噪声暴露后的早期变化（24小时内），探究内耳中的细胞死亡是否总是与JNK的磷酸化有关。将麻醉的成年白化大鼠暴露于单次脉冲噪声（194 kPa），并在3或24小时后处死。对石蜡包埋切片进行磷酸化JNK的阳性染色检查以及DNA片段化细胞（TUNEL染色）的存在情况检查。在脉冲噪声暴露后24小时，在螺旋缘和血管纹处观察到TUNEL阳性染色，但在这些部位未发现与JNK激活有相关性。在听觉器官（柯蒂氏器）和侧壁中，创伤后24小时观察到TUNEL反应性细胞。在此之前，在3小时时出现p-JNK染色，表明这些区域存在JNK激活的细胞死亡。最后，在螺旋神经节中观察到p-JNK反应性，在本研究的时间范围内与TUNEL染色无相关性。这些结果表明，脉冲噪声暴露后JNK的激活可能并不总是与细胞死亡相关，相反，一些细胞可能通过JNK非依赖性信号传导死亡。
