Department of Physiology and The Eisdell Moore Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
Department of Physiology and Translational Neuroscience Facility, School of Medical Sciences, UNSW, Sydney, NSW, 2052, Australia.
Histochem Cell Biol. 2018 Sep;150(3):281-289. doi: 10.1007/s00418-018-1683-8. Epub 2018 Jun 4.
Aminoglycoside ototoxicity results in permanent loss of the sensory hair cells in the mammalian cochlea. It usually begins at the basal turn causing high-frequency hearing loss. Here we describe previously unreported resistance of hair cells to neomycin ototoxicity in the extreme basal (hook) region of the developing cochlea of the C57BL/6 mouse. Organ of Corti explants from mice at postnatal day 3 were incubated (37 °C, 5% CO) in normal culture medium for 19.5 h prior to and after exposure to neomycin (1 mM, 3 h). To study neomycin uptake in the hair cells, cochlear explants were incubated with Neomycin Texas-red (NTR) conjugate. As expected, exposure to neomycin significantly reduced the survival of inner (IHC) and outer hair cells (OHC). IHC survival rate was high in the apical segment and low in the basal segment. OHC were well preserved in the apical and hook regions, with substantial OHC loss in the basal segment. The NTR uptake study demonstrated that the high survival rate in the extreme basal turn OHC was associated with low NTR uptake. Treatment with a calcium chelator (BAPTA), which disrupts the opening of mechanoelectrical (MET) transduction channels, abolished or reduced NTR uptake in the hair cells throughout the cochlea. This confirmed the essential role of MET channels in neomycin uptake and implied that the transduction channels could be impaired in the hook region of the developing mouse cochlea, possibly as a result of the cadherin 23 mutation responsible for the progressive deafness in C57BL/6 mice.
氨基糖苷类耳毒性会导致哺乳动物耳蜗中的感觉毛细胞永久性丧失。它通常从基底圈开始，导致高频听力损失。在这里，我们描述了以前未报道过的 C57BL/6 小鼠发育耳蜗极端基底（钩）区域毛细胞对新霉素耳毒性的抗性。在新霉素（1mM，3 小时）暴露之前和之后，将来自出生后第 3 天的小鼠的 Corti 器官外植体在正常培养基中（37°C，5% CO）孵育 19.5 小时。为了研究毛细胞中新霉素的摄取，用 Neomycin Texas-red（NTR）缀合物孵育耳蜗外植体。如预期的那样，新霉素暴露显著降低了内毛细胞（IHC）和外毛细胞（OHC）的存活率。IHC 在顶端段的存活率高，而在基底段的存活率低。OHC 在顶端和钩区域得到很好的保存，而在基底段则有大量 OHC 丧失。NTR 摄取研究表明，极端基底圈 OHC 的高存活率与低 NTR 摄取有关。用钙螯合剂（BAPTA）处理，破坏机械电（MET）转导通道的开放，可消除或减少整个耳蜗毛细胞中的 NTR 摄取。这证实了 MET 通道在新霉素摄取中的重要作用，并暗示在发育中的 C57BL/6 小鼠耳蜗的钩区域，转导通道可能受损，可能是由于导致 C57BL/6 小鼠进行性耳聋的钙粘蛋白 23 突变所致。
