Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
J Neuroimmunol. 2022 Nov 15;372:577971. doi: 10.1016/j.jneuroim.2022.577971. Epub 2022 Sep 15.
Perturbation of the endocannabinoid system can have profound effects on immune function and synaptic plasticity. Microglia are one of few cell types with a self-contained endocannabinoid system and are positioned at the interface between the immune system and the central nervous system. Past work has produced conflicting results with respect to the effects of pro-inflammatory conditions on the microglial endocannabinoid system. Thus, we systematically investigated the relationship between the concentration of two distinct pro-inflammatory stimuli, lipopolysaccharide and interferon gamma, on the abundance of components of the endocannabinoid system within microglia. Here we show that lipopolysaccharide and interferon gamma influence messenger RNA abundances of the microglial endocannabinoid system in a concentration-dependent manner. Furthermore, we demonstrate that the efficacy of different synthetic cannabinoid treatments with respect to inhibition of microglia nitric oxide release is dependent on the concentration and type of pro-inflammatory stimuli presented to the microglia. This indicates that different pro-inflammatory stimuli influence the capacity of microglia to synthesize, degrade, and respond to cannabinoids which has implications for the development of cannabinoid-based treatments for neuroinflammation.
内源性大麻素系统的紊乱会对免疫功能和突触可塑性产生深远的影响。小胶质细胞是少数具有自我内源性大麻素系统的细胞类型之一，位于免疫系统和中枢神经系统之间的界面上。过去的研究结果对于炎症条件对小胶质细胞内源性大麻素系统的影响存在矛盾。因此，我们系统地研究了两种不同的促炎刺激物——脂多糖和干扰素 γ——的浓度与小胶质细胞内源性大麻素系统成分丰度之间的关系。在这里，我们表明，脂多糖和干扰素 γ 以浓度依赖的方式影响小胶质细胞内源性大麻素系统的信使 RNA 丰度。此外，我们还证明了不同合成大麻素处理抑制小胶质细胞一氧化氮释放的效果取决于向小胶质细胞呈现的促炎刺激物的浓度和类型。这表明不同的促炎刺激物会影响小胶质细胞合成、降解和对大麻素作出反应的能力，这对开发基于大麻素的神经炎症治疗方法具有重要意义。
