小柯机器人

脊髓星形胶质细胞上的大麻素受体控制病理性震颤
2021-03-21 14:23

丹麦哥本哈根大学 Jean-Franois Perrier小组的一项最新研究发现,脊髓星形胶质细胞大麻素受体控制病理性震颤。这一研究成果发表在2021年3月18日出版的国际学术期刊《自然-神经科学》上。

研究人员发现受损及神经退行性疾病引起的震颤是由脊髓腹侧角星形胶质细胞上的大麻素受体介导,并在该区域开始交替的肢体运动。首先,研究人员发现在原发性震颤小鼠模型中,通过鞘内注射大麻素类似物WIN55,212-2可减少震颤。

研究人员利用电生理记录探究了脊髓切片的潜在机制,并发现去极化中间神经元释放的内源性大麻素激活了星形细胞上的大麻素受体,引起细胞内Ca2+增加,嘌呤后续释放和兴奋性神经传递的抑制。 最后,研究表明敲除星形胶质细胞中CB1受体后,WIN55,212-2在小鼠脊髓中的抗震颤作用受到抑制。

该研究数据表明,大麻素通过其对脊髓星形胶质细胞的作用而减少震颤。

据悉,大麻素可减轻受伤以及由神经退行性疾病引起的运动障碍相关的震颤。

附:英文原文

Title: Spinal astroglial cannabinoid receptors control pathological tremor

Author: Eva Maria Meier Carlsen, Sarah Falk, Urszula Skupio, Laurie Robin, Antonio C. Pagano Zottola, Giovanni Marsicano, Jean-Franois Perrier

Issue&Volume: 2021-03-18

Abstract: 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 Ca2+, 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 CB1 receptors in astrocytes. Our data suggest that cannabinoids reduce tremor via their action on spinal astrocytes. Astrocytes regulate synaptic transmission. Carlsen et al. report that spinal astrocytes activated by endocannabinoids inhibit excitatory synaptic transmission and, thereby, decrease tremor.

DOI: 10.1038/s41593-021-00818-4

Source: https://www.nature.com/articles/s41593-021-00818-4

 

Nature Neuroscience:《自然—神经科学》,创刊于1998年。隶属于施普林格·自然出版集团,最新IF:28.771
官方网址:https://www.nature.com/neuro/
投稿链接:https://mts-nn.nature.com/cgi-bin/main.plex


本期文章:《自然—神经科学》:Online/在线发表

分享到:

0