Institute for Molecular Psychiatry, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.
International Max Planck Research School for Brain and Behavior, University of Bonn, 53175 Bonn, Germany.
Int J Mol Sci. 2020 Dec 22;22(1):19. doi: 10.3390/ijms22010019.
Microglia are key to maintaining the homeostasis of the brain. These immune cells of the brain can be our biggest ally in fighting infections, but can worsen pathology or hinder recovery when uncontrolled. Thus, understanding how microglia contribute to neuroinflammatory processes and how their activity can be controlled is of great importance. It is known that activation of endocannabinoid system, and especially the cannabinoid type 2 receptor (CB2R), decreases inflammation. Alongside its non-psychoactive effect, it makes the CB2R receptor a perfect target for treating diseases accompanied by neuroinflammation including neurodegenerative diseases. However, the exact mechanisms by which CB2R regulates microglial activity are not yet understood. Here, we review the current knowledge on the roles of microglial CB2R from in vitro and in vivo studies. We look into CB2R function under physiological and pathological conditions and focus on four different disease models representing chronic and acute inflammation. We highlight open questions and controversies and provide an update on the latest discoveries that were enabled by the development of novel technologies. Also, we discuss the recent findings on the role of microglia CB2R in cognition and its role in neuron-microglia communication.
小胶质细胞是维持大脑内环境稳定的关键。这些大脑中的免疫细胞可以成为我们对抗感染的最大盟友，但如果不受控制，它们可能会加重病理或阻碍恢复。因此，了解小胶质细胞如何参与神经炎症过程以及如何控制它们的活性非常重要。已知内源性大麻素系统的激活，特别是大麻素受体 2（CB2R），可以减少炎症。除了其非精神活性作用外，这使得 CB2R 受体成为治疗伴有神经炎症的疾病（包括神经退行性疾病）的理想靶点。然而，CB2R 调节小胶质细胞活性的确切机制尚不清楚。在这里，我们回顾了来自体外和体内研究的小胶质细胞 CB2R 的现有知识。我们研究了 CB2R 在生理和病理条件下的功能，并重点关注了四个不同的疾病模型，代表慢性和急性炎症。我们强调了悬而未决的问题和争议，并提供了最新发现的更新，这些发现得益于新技术的发展。此外，我们还讨论了小胶质细胞 CB2R 在认知中的作用及其在神经元-小胶质细胞通讯中的作用的最新发现。
