Ayako Ajima1, Takamasa Yoshida2, Kunio Yaguchi3, Shigeyoshi Itohara3. 1. Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako, Saitama, Japan; Laboratory for Systems Molecular Ethology, RIKEN Center for Brain Science, Wako, Saitama, Japan. Electronic address: aayako@riken.jp. 2. Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako, Saitama, Japan; Department of Biomedical Engineering, Faculty of Science and Engineering, Toyo University, Kawagoe, Saitama, Japan. Electronic address: yoshida083@toyo.jp. 3. Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako, Saitama, Japan.
Abstract
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.
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.