Department of Otolaryngology, Eiju General Hospital, 2-23-16 Higashi-ueno, Taito-ku, Tokyo 110-8645, Japan; The Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan; Department of Otolaryngology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Neurosci Res. 2013 Sep-Oct;77(1-2):33-41. doi: 10.1016/j.neures.2013.06.003. Epub 2013 Jul 1.
Fibrocytes in the cochlear lateral wall and spiral limbus play an important role in transporting K(+) and have the capacity of self-renewal. We showed that acute energy failure in the rat cochlea induced by local administration of the mitochondrial toxin 3-nitropropionic acid (3NP) caused hearing loss in a concentration-dependent manner, mainly due to degeneration of cochlear fibrocytes. We produced long-lasting profound cochlear damage in this model by modifying the 3NP administration protocol and observed morphological changes at 16 weeks after the administration. In the spiral ligament, severe degeneration of fibrocytes was observed in the basal turn, and the levels of the Na,K-ATPase alpha and beta1 subunits and of NKCC1 were decreased in these cells, whereas connexin 26 (Cx26) level increased in the type 1 fibrocytes adjacent to the stria vascularis. In the stria vascularis, levels of Kir4.1 and L-PGDS decreased. In the spiral limbus, severe degeneration of fibrocytes was observed in the middle and basal turns, but NKCC1 and Cx26 were still found in the center of the limbus in the middle turn. These results indicate long-lasting changes in the cochlear lateral wall and spiral limbus, which may compensate for damaged K(+) recycling and protect cells from ATP shortage.
耳蜗侧壁和螺旋缘中的纤维细胞在转运 K+方面发挥着重要作用，并且具有自我更新的能力。我们表明，局部给予线粒体毒素 3-硝基丙酸（3NP）可导致大鼠耳蜗内急性能量衰竭，从而导致浓度依赖性听力损失，主要是由于耳蜗纤维细胞的变性。通过修改 3NP 给药方案，我们在该模型中产生了持久的严重耳蜗损伤，并在给药后 16 周观察到形态学变化。在螺旋韧带中，基底回的纤维细胞发生严重变性，这些细胞中 Na,K-ATPase α和β1 亚基和 NKCC1 的水平降低，而相邻于血管纹的 1 型纤维细胞中连接蛋白 26（Cx26）水平增加。在血管纹中，Kir4.1 和 L-PGDS 的水平降低。在螺旋缘中，中回和底回的纤维细胞发生严重变性，但在中回的缘中心仍发现 NKCC1 和 Cx26。这些结果表明耳蜗侧壁和螺旋缘发生了持久变化，这可能补偿了受损的 K+再循环，并保护细胞免受 ATP 短缺的影响。
