Department of Physiology, Faculty of Medicine, Demiroglu Bilim University, Istanbul, Turkey.
Kocaeli University, Faculty of Medicine, Department of Pharmacology, Kocaeli, Turkey.
Neurosci Lett. 2021 May 14;753:135881. doi: 10.1016/j.neulet.2021.135881. Epub 2021 Apr 7.
Essential tremor (ET) is one of the most prevalent movement disorders and the most common cause of abnormal tremors. However, it cannot be treated efficiently with the currently available pharmacotherapy options. The pathophysiology of harmaline-induced tremor, most commonly used model of ET, involves various neurotransmitter systems including glutamate as well as ion channels. Agmatine, an endogenous neuromodulator, interacts with various glutamate receptor subtypes and ion channels, which have been associated with its' beneficial effects on several neurological disorders. The current study aims to assess the effect of agmatine on the harmaline model of ET. Two separate groups of male rats were injected either with saline or agmatine (40 mg/kg) 30 min prior to single intraperitoneal injection of harmaline (20 mg/kg). The percent duration, intensity and frequency of tremor and locomotor activity were evaluated by a custom-built tremor and locomotion analysis system. Pretreatment with agmatine reduced the percent tremor duration and intensity of tremor induced by harmaline, without affecting the tremor frequency. However, it did not affect the decreased spontaneous locomotor activity due to harmaline. This pattern of ameliorating effects of agmatine on harmaline-induced tremor provide the first evidence for being considered as a treatment option for ET.
特发性震颤(essential tremor,ET)是最常见的运动障碍之一,也是异常震颤最常见的原因。然而,目前可用的药物治疗选择并不能有效地治疗 ET。哈尔马琳诱导的震颤的病理生理学,最常用的 ET 模型,涉及多种神经递质系统,包括谷氨酸以及离子通道。胍丁胺是一种内源性神经调节剂,与各种谷氨酸受体亚型和离子通道相互作用,这与其对几种神经退行性疾病的有益作用有关。本研究旨在评估胍丁胺对哈尔马琳诱导的 ET 模型的影响。两组雄性大鼠分别在单次腹腔注射哈尔马琳(20mg/kg)前 30 分钟注射生理盐水或胍丁胺(40mg/kg)。通过定制的震颤和运动分析系统评估震颤的持续时间、强度和频率以及运动活动的百分比。胍丁胺预处理可减少哈尔马琳诱导的震颤的持续时间和强度百分比,而不影响震颤频率。然而,它并没有影响因哈尔马琳引起的自发运动活动的减少。胍丁胺对哈尔马琳诱导的震颤的这种改善作用模式为将其作为 ET 的治疗选择提供了第一个证据。