Background

Essential tremor is the most prevalent movement disorder and is thought to be caused by abnormalities in the cerebellar system; however, its underlying neural mechanism is poorly understood. In this study, we found that mice lacking netrin-G2, a cell adhesion molecule which is expressed in neural circuits related to the cerebellar system, exhibited a microtremor resembling an essential tremor. However, it was difficult to quantify microtremors in netrin-G2 KO mice.

New Method

We developed a new tremor detector which can quantify the intensity and frequency of a tremor.

Results

Using this system, we were able to characterize both the microtremors in netrin-G2 KO mice and low-dose harmaline-induced tremors which, to date, had been difficult to detect. Alcohol and anti-tremor drugs, which are effective in decreasing the symptoms of essential tremor in patients, were examined in netrin-G2 KO mice. We found that some drugs lowered the tremor frequency, but had little effect on tremor intensity. Forced swim as a stress stimulus in netrin-G2 KO mice dramatically enhanced tremor symptoms.

Comparison with Existing Methods

The detection performance even for tremors induced by low-dose harmaline was similar to that in previous studies or more sensitive than the others.

Conclusions

Microtremors in netrin-G2 KO mice are reliably and quantitatively detected by our new tremor detection system. We found different effects of medicines and factors between human essential tremors and microtremors in netrin-G2 KO mice, suggesting that the causations, mechanisms, and symptoms of tremors vary and are heterogeneous, and the objective analyses are required.

中文翻译：

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netrin-G2基因敲除小鼠微震的客观检测

背景

特发性震颤是最普遍的运动障碍，被认为是由小脑系统异常引起的；然而，人们对其潜在的神经机制知之甚少。在这项研究中，我们发现缺乏 netrin-G2（一种在与小脑系统相关的神经回路中表达的细胞粘附分子）的小鼠表现出类似于特发性震颤的微震。然而，很难量化 netrin-G2 KO 小鼠的微颤。

新方法

我们开发了一种新的震颤检测器，可以量化震颤的强度和频率。

结果

使用该系统，我们能够表征 netrin-G2 KO 小鼠的微震和迄今为止难以检测到的低剂量哈马林诱发的震颤。在 netrin-G2 KO 小鼠中检测了可有效减轻患者特发性震颤症状的酒精和抗震颤药物。我们发现一些药物降低了震颤频率，但对震颤强度影响不大。强迫游泳作为 netrin-G2 KO 小鼠的压力刺激显着增强了震颤症状。

与现有方法的比较

即使对低剂量哈马林引起的震颤的检测性能也与以前的研究相似或比其他研究更敏感。

结论

netrin-G2 KO 小鼠的微震通过我们的新震颤检测系统可靠且定量地检测。我们在netrin-G2 KO小鼠中发现人类特发性震颤和微震之间药物和因素的不同影响，表明震颤的病因、机制和症状各不相同且异质，需要客观分析。