Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Center Laboratories, Jinshan Hospital of Fudan University, Shanghai 201508, China.
Neurobiol Dis. 2022 Jul;169:105743. doi: 10.1016/j.nbd.2022.105743. Epub 2022 Apr 28.
Depression is one of the most prevalent mental illnesses in the world today, and the onset of depression is usually accompanied by neuroinflammation and impaired adult neurogenesis. As a new potential member of the endocannabinoid (eCB) system, G protein coupled receptor 55 (GPR55) has been associated with mood regulation. However, the role of GPR55 in the pathophysiology of depression remains poorly understood. Thus, a 10-day chronic social defeat stress (CSDS) paradigm was utilized as an animal model of depression to explore the potential role of GPR55 in depression. After CSDS, the protein level of GPR55 decreased significantly, but the mRNA expression did not change significantly, highlighting that although the GPR55 protein was involved in the progression of the depression- and anxiety-like phenotypes, its mRNA was not. Additionally, depression- and anxiety-like behaviors were also accompanied by neuroinflammation and impaired adult neurogenesis in the hippocampus. Interestingly, O-1602, a GPR55 agonist, remarkably prevented the development of depression- and anxiety-like behaviors as well as hippocampal neuroinflammation and neurogenesis deficits induced by CSDS. However, after electroacupuncture (EA) alleviated depression- and anxiety-like behaviors induced by CSDS, treatment with a GPR55 antagonist (CID16020046) reversed this effect. Our research demonstrated that downregulation of GPR55 expression in the hippocampus might mediate CSDS-induced depression- and anxiety-like phenotypes, and activation and upregulation of GPR55, which might be correlated with its anti-inflammatory and subsequent neuroprotective effects, could be a potential treatment for depression.
抑郁症是当今世界上最普遍的精神疾病之一，抑郁症的发作通常伴随着神经炎症和成年神经发生受损。作为内源性大麻素（eCB）系统的新潜在成员，G 蛋白偶联受体 55（GPR55）与情绪调节有关。然而，GPR55 在抑郁症发病机制中的作用仍知之甚少。因此，采用 10 天慢性社会挫败应激（CSDS）范式作为抑郁症动物模型，探讨 GPR55 在抑郁症中的潜在作用。CSDS 后，GPR55 蛋白水平显著下降，但 mRNA 表达无明显变化，这表明尽管 GPR55 蛋白参与了抑郁症和焦虑样表型的进展，但它的 mRNA 没有。此外，抑郁症和焦虑样行为也伴随着海马体中的神经炎症和成年神经发生受损。有趣的是，GPR55 激动剂 O-1602 显著预防了 CSDS 诱导的抑郁症和焦虑样行为以及海马体神经炎症和神经发生缺陷的发展。然而，电针（EA）缓解 CSDS 诱导的抑郁症和焦虑样行为后，用 GPR55 拮抗剂（CID16020046）处理会逆转这种效果。我们的研究表明，海马体中 GPR55 表达的下调可能介导 CSDS 诱导的抑郁症和焦虑样表型，而 GPR55 的激活和上调可能与它的抗炎和随后的神经保护作用相关，可能成为治疗抑郁症的一种潜在方法。
