Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, 1250 Moursund Street, Suite 1325, Houston, TX 77030, USA.
Cells. 2022 Dec 1;11(23):3889. doi: 10.3390/cells11233889.
Tremor is the most common movement disorder. Several drugs reduce tremor severity, but no cures are available. Propranolol, a β-adrenergic receptor blocker, is the leading treatment for tremor. However, the in vivo circuit mechanisms by which propranolol decreases tremor remain unclear. Here, we test whether propranolol modulates activity in the cerebellum, a key node in the tremor network. We investigated the effects of propranolol in healthy control mice and mice, which exhibit pathophysiological tremor and ataxia due to cerebellar dysfunction. Propranolol reduced physiological tremor in control mice and reduced pathophysiological tremor in mice to control levels. Open field and footprinting assays showed that propranolol did not correct ataxia in mice. In vivo recordings in awake mice revealed that propranolol modulates the spiking activity of control and Purkinje cells. Recordings in cerebellar nuclei neurons, the targets of Purkinje cells, also revealed altered activity in propranolol-treated control and mice. Next, we tested whether propranolol reduces tremor through β and β adrenergic receptors. Propranolol did not change tremor amplitude or cerebellar nuclei activity in β and β null mice or mice lacking β and β receptor function. These data show that propranolol can modulate cerebellar circuit activity through β-adrenergic receptors and may contribute to tremor therapeutics.
震颤是最常见的运动障碍。一些药物可降低震颤严重程度，但尚无治愈方法。普萘洛尔是一种β肾上腺素能受体阻滞剂，是治疗震颤的主要药物。然而，普萘洛尔降低震颤的体内回路机制尚不清楚。在这里，我们测试普萘洛尔是否调节小脑的活动，小脑是震颤网络的关键节点。我们研究了普萘洛尔对健康对照小鼠和 小鼠的影响，这些小鼠由于小脑功能障碍而表现出生理震颤和共济失调。普萘洛尔降低了对照小鼠的生理性震颤，并将 小鼠的病理性震颤降低至对照水平。旷场和足迹分析表明，普萘洛尔不能纠正 小鼠的共济失调。在清醒小鼠的体内记录显示，普萘洛尔调节对照和 小鼠浦肯野细胞的放电活动。小脑核神经元（浦肯野细胞的靶标）的记录也显示出普萘洛尔处理的对照和 小鼠的活性改变。接下来，我们测试了普萘洛尔是否通过β和β肾上腺素能受体来降低震颤。在β和β缺失小鼠或缺乏β和β受体功能的 小鼠中，普萘洛尔并未改变震颤幅度或小脑核活动。这些数据表明，普萘洛尔可以通过β肾上腺素能受体调节小脑回路活动，并可能有助于震颤治疗。
