Muly S M, Gross J S, Potashner S J
Department of Neuroscience, University of Connecticut Health Center, Farmington, 06030-3401, USA.
J Neurosci Res. 2004 Feb 15;75(4):585-96. doi: 10.1002/jnr.20011.
Exposure of adults to loud noise can overstimulate the auditory system, damage the cochlea, and destroy cochlear nerve axons and their synaptic endings in the brain. Cochlear nerve loss probably results from the death of cochlear inner hair cells (IHC). Additional degeneration in the cochlear nucleus (CN) is hypothesized to stem from overstimulation of the system, which may produce excitotoxicity. This study tested these predictions by exposing one ear of anesthetized adult chinchillas to a loud noise, which damaged the ipsilateral cochlea and induced degeneration in the glutamatergic cochlear nerve. During the first postexposure week, before cochlear nerve axons degenerated, glutamatergic synaptic release in the ipsilateral CN was elevated and uptake was depressed, consistent with hyperactivity of glutamatergic transmission and perhaps with the operation of an excitotoxic mechanism. By 14 days, when cochlear nerve fibers degenerated, glutamatergic synaptic release and uptake in the CN became deficient. By 90 days, a resurgence of transmitter release and an elevation of AMPA receptor binding suggested transmission upregulation through plasticity that resembled changes after mechanical cochlear damage. These changes may contribute to tinnitus and other pathologic symptoms that precede and accompany hearing loss. In contrast, the other ear, protected with a silicone plug during the noise exposure, exhibited virtually no damage in the cochlea or the cochlear nerve. Altered glutamatergic release and AMPA receptor binding activity in the CN suggested upregulatory plasticity driven by signals emanating from the CN on the noise-exposed side.
成年人暴露于高强度噪音会过度刺激听觉系统，损害耳蜗，并破坏耳蜗神经轴突及其在大脑中的突触末梢。耳蜗神经损伤可能是由耳蜗内毛细胞（IHC）死亡导致的。耳蜗核（CN）的额外退化被认为源于系统的过度刺激，这可能会产生兴奋性毒性。本研究通过将麻醉的成年龙猫的一只耳朵暴露于高强度噪音中来验证这些预测，这种噪音会损害同侧耳蜗并导致谷氨酸能耳蜗神经退化。在暴露后的第一周，在耳蜗神经轴突退化之前，同侧CN中的谷氨酸能突触释放增加，摄取减少，这与谷氨酸能传递的过度活跃一致，可能也与兴奋性毒性机制的运作有关。到第14天，当耳蜗神经纤维退化时，CN中的谷氨酸能突触释放和摄取变得不足。到90天时，递质释放的恢复和AMPA受体结合的增加表明通过可塑性实现了传递上调，这类似于机械性耳蜗损伤后的变化。这些变化可能导致耳鸣和其他在听力损失之前及伴随出现的病理症状。相比之下，另一只在噪音暴露期间用硅胶塞保护的耳朵，在耳蜗或耳蜗神经中几乎没有损伤。CN中谷氨酸能释放和AMPA受体结合活性的改变表明，由噪音暴露侧的CN发出的信号驱动了上调可塑性。
