Milbrandt J C, Holder T M, Wilson M C, Salvi R J, Caspary D M
Southern Illinois University School of Medicine, Pharmacology Department, 801 N Rutledge St., P.O. Box 19629, Springfield, IL 62794-9629, USA.
Hear Res. 2000 Sep;147(1-2):251-60. doi: 10.1016/s0378-5955(00)00135-0.
Pharmacological studies of the inferior colliculus (IC) suggest that the inhibitory amino acid neurotransmitter gamma-aminobutyric acid (GABA) plays an important role in shaping responses to simple and complex acoustic stimuli. Several models of auditory dysfunction, including age-related hearing loss, tinnitus, and peripheral deafferentation, suggest an alteration of normal GABA neurotransmission in central auditory pathways. The present study attempts to further characterize noise-induced changes in GABA markers in the IC. Four groups (unexposed control, 0 h post-exposure, 42 h post-exposure, and 30 days post-exposure) of 3-month-old male Fischer 344 rats were exposed to a high intensity sound (12 kHz, 106 dB) for 10 h. Observed hair cell damage was primarily confined to the basal half of the cochlea. There was a significant decrease in glutamic acid decarboxylase (GAD(65)) immunoreactivity in the IC membrane fraction compared to controls (P<0.05) at 0 h (-41%) and 42 h (-28%) post-exposure, with complete recovery by 30 days post-exposure (P>0.98). Observed decreases in cytosolic levels of GAD(65) were not significant. Quantitative muscimol receptor binding revealed a significant increase (+20%) in IC 30 days after sound exposure (P<0.05). These data suggest that changes in GABA neurotransmission occur in the IC of animals exposed to intense sound. Additional studies are needed to determine whether these changes are a result of protective/compensatory mechanisms or merely peripheral differentiation, as well as whether these changes preserve or diminish central auditory system function.
下丘（IC）的药理学研究表明，抑制性氨基酸神经递质γ-氨基丁酸（GABA）在塑造对简单和复杂听觉刺激的反应中起重要作用。几种听觉功能障碍模型，包括年龄相关性听力损失、耳鸣和外周去传入，提示中枢听觉通路中正常的GABA神经传递发生改变。本研究试图进一步描述噪声诱导的IC中GABA标志物的变化。将四组（未暴露对照组、暴露后0小时、暴露后42小时和暴露后30天）3月龄雄性Fischer 344大鼠暴露于高强度声音（12 kHz，106 dB）10小时。观察到的毛细胞损伤主要局限于耳蜗的基部一半。与对照组相比，暴露后0小时（-41%）和42小时（-28%）时，IC膜部分的谷氨酸脱羧酶（GAD(65)）免疫反应性显著降低（P<0.05），暴露后30天完全恢复（P>0.98）。观察到的GAD(65)胞质水平降低不显著。定量蝇蕈醇受体结合显示，声音暴露30天后IC中显著增加（+20%）（P<0.05）。这些数据表明，暴露于高强度声音的动物的IC中发生了GABA神经传递的变化。需要进一步研究以确定这些变化是保护性/补偿性机制的结果还是仅仅是外周分化，以及这些变化是保留还是损害中枢听觉系统功能。
