Targeting inhibitory neurotransmission in tinnitus.
Targeting inhibitory neurotransmission in tinnitus.
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DOI：
10.1016/j.brainres.2012.02.014
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发表时间：
2012-11-16
期刊：
影响因子：
2.9
通讯作者：
Caspary DM
中科院分区：
文献类型：
--
作者：
Richardson BD;Brozoski TJ;Ling LL;Caspary DM
听觉感知依赖于听觉神经轴和相关结构内的神经相关物的存在。耳鸣的危害有哪些？耳鸣的危害有哪些？一种方法是上调内源性抑制性神经递质水平（例如甘氨酸和GABA）并选择性靶向关键回路中的抑制性受体以使耳鸣病理生理正常化。因此，两个主要的配体门控抑制性受体系统，GABAA受体（GABAAR）和甘氨酸受体（GlyR）的基本功能和分子特性的描述。还审查了靶向抑制的基本原理，这源于报告耳鸣相关的稳态可塑性的抑制性神经递质系统和相关的增强神经元的兴奋性，在大多数中央听觉结构。然而，内侧膝状体（MGB）在耳鸣中的假定作用尚未得到解决，特别是在其抑制性传入下丘和丘脑网状核及其GABAAR功能的异质性。GABAAR的这种异质性群体，可能在耳鸣病理学中改变，及其在听觉CNS中的关键解剖位置，使MGB成为耳鸣研究的一个引人注目的结构。最后，一些选择性的化合物，增强紧张性抑制，已成功地改善耳鸣的动物研究，这表明，MGB，并在较小程度上，听觉皮层可能是他们的主要作用部位。这些药理学干预检查，在其作用机制和为什么这些药物，可能是有效的耳鸣治疗方面。
Tinnitus perception depends on the presence of its neural correlates within the auditory neuraxis and associated structures. Targeting specific circuits and receptors within the central nervous system in an effort to relieve the perception of tinnitus and its impact on one’s emotional and mental state has become a focus of tinnitus research. One approach is to upregulate endogenous inhibitory neurotransmitter levels (e.g. glycine and GABA) and selectively target inhibitory receptors in key circuits to normalize tinnitus pathophysiology. Thus, the basic functional and molecular properties of two major ligand-gated inhibitory receptor systems, the GABAA receptor (GABAAR) and glycine receptor (GlyR) are described. Also reviewed is the rationale for targeting inhibition which stems from reported tinnitus-related homeostatic plasticity of inhibitory neurotransmitter systems and associated enhanced neuronal excitability throughout most central auditory structures. However, the putative role of the medial geniculate body (MGB) in tinnitus has not been previously addressed, specifically in terms of its inhibitory afferents from inferior colliculus and thalamic reticular nucleus and its GABAAR functional heterogeneity. This heterogeneous population of GABAARs, which may be altered in tinnitus pathology, and its key anatomical position in the auditory CNS make the MGB a compelling structure for tinnitus research. Finally, some selective compounds, which enhance tonic inhibition, have successfully ameliorated tinnitus in animal studies, suggesting that the MGB and, to a lesser degree, the auditory cortex may be their primary locus of action. These pharmacological interventions are examined, in terms of their mechanism of action and why these agents, may be effective in tinnitus treatment.
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影响因子：
2.6
作者：
Bauer, CA;Brozoski, TJ
通讯作者：
Brozoski, TJ
DOI：
10.1007/s101620010030
发表时间：
2001-03-01
影响因子：
2.4
作者：
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通讯作者：
Brozoski, TJ
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作者：
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通讯作者：
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影响因子：
3.5
作者：
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通讯作者：
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影响因子：
3.3
作者：
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通讯作者：
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