Plasticity at glycinergic synapses in dorsal cochlear nucleus of rats with behavioral evidence of tinnitus.
Plasticity at glycinergic synapses in dorsal cochlear nucleus of rats with behavioral evidence of tinnitus.
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DOI：
10.1016/j.neuroscience.2009.08.026
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发表时间：
2009-12-01
期刊：
影响因子：
3.3
通讯作者：
Caspary, D. M.
中科院分区：
文献类型：
--
作者：
Wang, H.;Brozoski, T. J.;Turner, J. G.;Ling, L.;Parrish, J. L.;Hughes, L. F.;Caspary, D. M.
15% 到 35% 的美国人有耳鸣的经历，这是一种主观的“耳鸣”。高达 10% 的患者报告有严重的致残症状。使用单侧、一小时、以 17 kHz 为中心的倍频程噪声 (116 dB SPL) 诱导大鼠耳鸣，并使用间隙惊吓法进行评估。耳蜗背核（DCN）被认为经历了塑性变化，表明耳鸣发展过程中抑制功能发生了改变。暴露的大鼠在暴露后 16 周的咔嗒声和所有测试频率均接近暴露前 ABR 阈值。暴露于声音的大鼠在暴露于声音 16 周后，在 24 kHz 和 32 kHz 下的间隙检测明显较差，表明出现了慢性高频耳鸣。声音暴露 4 个月后，在 DCN 梭形细胞中测量了 α1-3 和 β 甘氨酸受体亚基 (GlyR) 以及锚定蛋白 gephyrin 的信息和蛋白质水平。有耳鸣证据的大鼠显示，DCN 中频和高频区域的 GlyR α1 蛋白显着减少，而 α1 信息水平却相反地增加。在暴露于声音的大鼠中，Gephyrin 水平显示出与耳鸣相关的显着增加，表明暴露于声音后细胞内受体运输发生变化。与 α1 亚基蛋白水平降低一致，马钱子碱结合研究显示耳鸣相关的 GlyR 结合位点数量显着减少，支持耳鸣相关的 GlyR 数量和/或组成变化。总的来说，这些发现表明耳鸣的发生可能与 DCN 梭形细胞中功能性 GlyR 的变化有关，这与之前描述的行为和神经生理学变化一致。耳鸣相关的 GlyR 变化可以为耳鸣药物治疗或阻断耳鸣发生提供独特的受体靶点。
Fifteen to 35% of the United States population experiences tinnitus, a subjective “ringing in the ears”. Up to 10 percent of those afflicted report severe and disabling symptoms. Tinnitus was induced in rats using unilateral, one-hour, 17 kHz-centered octave-band noise (116 dB SPL) and assessed using a gap-startle method. The dorsal cochlear nucleus (DCN) is thought to undergo plastic changes suggestive of altered inhibitory function during tinnitus development. Exposed rats showed near pre-exposure ABR thresholds for clicks and all tested frequencies 16 weeks post-exposure. Sound-exposed rats showed significantly worse gap detection at 24 and 32 kHz 16 weeks following sound exposure, suggesting the development of chronic, high frequency tinnitus. Message and protein levels of α1–3, and β glycine receptor subunits (GlyRs), and the anchoring protein, gephyrin, were measured in DCN fusiform cells 4 months following sound exposure. Rats with evidence of tinnitus showed significant GlyR α1 protein decreases in the middle and high frequency regions of the DCN while α1 message levels were paradoxically increased. Gephyrin levels showed significant tinnitus-related increases in sound-exposed rats suggesting intracellular receptor trafficking changes following sound exposure. Consistent with decreased α1 subunit protein levels, strychnine binding studies showed significant tinnitus-related decreases in the number of GlyR binding sites, supporting tinnitus-related changes in the number and/or composition of GlyRs. Collectively, these findings suggest the development of tinnitus is likely associated with functional GlyR changes in DCN fusiform cells consistent with previously described behavioral and neurophysiologic changes. Tinnitus related GlyR changes could provide a unique receptor target for tinnitus pharmacotherapy or blockade of tinnitus initiation.
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DOI：
10.1007/s101620010030
发表时间：
2001-03-01
影响因子：
2.4
作者：
Bauer, CA;Brozoski, TJ
通讯作者：
Brozoski, TJ
影响因子：
--
作者：
BETZ, H;KUHSE, J;RAMMING, M
通讯作者：
RAMMING, M
影响因子：
2.9
作者：
Bush, Angela L.;Hyson, Richard L.
通讯作者：
Hyson, Richard L.
影响因子：
1.6
作者：
Fraenkel, R;Freeman, S;Sohmer, H
通讯作者：
Sohmer, H
影响因子：
2.8
作者：
Brozoski, TJ;Bauer, CA
通讯作者：
Bauer, CA