Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Nat Neurosci. 2021 May;24(5):658-666. doi: 10.1038/s41593-021-00818-4. Epub 2021 Mar 18.
Cannabinoids reduce tremor associated with motor disorders induced by injuries and neurodegenerative disease. Here we show that this effect is mediated by cannabinoid receptors on astrocytes in the ventral horn of the spinal cord, where alternating limb movements are initiated. We first demonstrate that tremor is reduced in a mouse model of essential tremor after intrathecal injection of the cannabinoid analog WIN55,212-2. We investigate the underlying mechanism using electrophysiological recordings in spinal cord slices and show that endocannabinoids released from depolarized interneurons activate astrocytic cannabinoid receptors, causing an increase in intracellular Ca, subsequent release of purines and inhibition of excitatory neurotransmission. Finally, we show that the anti-tremor action of WIN55,212-2 in the spinal cords of mice is suppressed after knocking out CB receptors in astrocytes. Our data suggest that cannabinoids reduce tremor via their action on spinal astrocytes.
大麻素可减少因损伤和神经退行性疾病引起的运动障碍相关的震颤。在这里，我们表明这种效果是由脊髓腹角星形胶质细胞上的大麻素受体介导的，而交替的肢体运动就是由这里发起的。我们首先证明，鞘内注射大麻素类似物 WIN55,212-2 后，原发性震颤小鼠模型中的震颤减少。我们使用脊髓切片中的电生理记录来研究潜在的机制，并表明去极化中间神经元释放的内源性大麻素激活星形胶质细胞上的大麻素受体，导致细胞内 Ca2+增加，随后嘌呤释放并抑制兴奋性神经传递。最后，我们表明，在星形胶质细胞中敲除 CB 受体后，WIN55,212-2 在小鼠脊髓中的抗震颤作用受到抑制。我们的数据表明，大麻素通过其对脊髓星形胶质细胞的作用来减少震颤。
