From neurons to neuron neighborhoods: the rewiring of the cerebellar cortex in essential tremor.
From neurons to neuron neighborhoods: the rewiring of the cerebellar cortex in essential tremor.
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DOI：
10.1007/s12311-013-0545-0
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发表时间：
2014-08
期刊：
影响因子：
3.5
通讯作者：
Louis, Elan D.
中科院分区：
文献类型：
--
作者：
Louis, Elan D.
尽管特发性震颤（ET）患病率很高，但关于其生物学方面的著述却少得惊人。橄榄体模型于20世纪70年代首次提出，是特发性震颤的传统疾病模型；然而，由于多种原因，该模型存在问题。最近，基于组织的深入研究已经在大多数特发性震颤病例的大脑中发现了一系列结构变化，且几乎所有观察到的变化都位于小脑皮质。这些研究表明，浦肯野细胞是特发性震颤发病机制的核心，因此可能为开发新的治疗策略提供重点。基于这些研究，一种新的特发性震颤模型提出，浦肯野细胞群是导致特发性震颤的初始分子/细胞事件的发生部位。此外，在分子层和颗粒层（即浦肯野细胞“周边”）观察到的许多继发性变化/重塑可能具有额外的机制重要性。在生理层面，重塑的存在表明特发性震颤中可能形成异常突触以及新的/异常的皮质回路。需要专门致力于理解特发性震颤中浦肯野细胞层及其神经元周边发生的生化和细胞事件级联，以及特发性震颤中该大脑区域可能发生的继发性重塑/重新布线的生理效应。
Remarkably little has been written on the biology of essential tremor (ET), despite its high prevalence. The olivary model, first proposed in the 1970s, is the traditional disease model for ET; however, the model is problematic for a number of reasons. Recently, intensive tissue-based studies have identified a series of structural changes in the brains of most ET cases, and nearly all of the observed changes are located in the cerebellar cortex. These studies suggest that Purkinje cells are central to the pathogenesis of ET and may thus provide a focus for the development of novel therapeutic strategies. Arising from these studies, a new model of ET proposes that the population of Purkinje cells represents the site of the initial molecular/cellular events leading to ET. Furthermore, a number of secondary changes/remodeling observed in the molecular and granular layers (i.e., in the Purkinje cell “neighborhood”) are likely to be of additional mechanistic importance. On a physiological level, the presence of remodeling indicates the likely formation of aberrant synapses and the creation of new/abnormal cortical circuits in ET. Specific efforts need to be devoted to understanding the cascade of biochemical and cellular events occurring in the Purkinje cell layer in ET and its neuron neighborhood, as well as the physiological effects of secondary remodeling/rewiring that are likely to be occurring in this brain region in ET.
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