Jiang Jian, Ju Jun, Luo Liang, Song Ze, Liao Huanquan, Yang Xiuyan, Wei Shoupeng, Wang Dilong, Zhu Wenhui, Chang Jinlong, Ma Junzhe, Hu Hao, Yu Jiezhong, Wang Huiqing, Hou Sheng-Tao, Li Shupeng, Li Huiliang, Li Ningning
Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
Department of Critical Care Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
Front Pharmacol. 2022 Feb 14;13:826055. doi: 10.3389/fphar.2022.826055. eCollection 2022.
Depressive disorder is defined as a psychiatric disease characterized by the core symptoms of anhedonia and learned helplessness. Currently, the treatment of depression still calls for medications with high effectiveness, rapid action, and few side effects, although many drugs, including fluoxetine and ketamine, have been approved for clinical usage by the Food and Drug Administration (FDA). In this study, we focused on calcitonin as an amylin receptor polypeptide, of which the antidepressant effect has not been reported, even if calcitonin gene-related peptides have been previously demonstrated to improve depressive-like behaviors in rodents. Here, the antidepressant potential of salmon calcitonin (sCT) was first evaluated in a chronic restraint stress (CRS) mouse model of depression. We observed that the immobility duration in CRS mice was significantly increased during the tail suspension test and forced swimming test. Furthermore, a single administration of sCT was found to successfully rescue depressive-like behaviors in CRS mice. Lastly, AC187 as a potent amylin receptor antagonist was applied to investigate the roles of amylin receptors in depression. We found that AC187 significantly eliminated the antidepressant effects of sCT. Taken together, our data revealed that sCT could ameliorate a depressive-like phenotype probably the amylin signaling pathway. sCT should be considered as a potential therapeutic candidate for depressive disorder in the future.
抑郁症被定义为一种以快感缺失和习得性无助为核心症状的精神疾病。目前，尽管包括氟西汀和氯胺酮在内的许多药物已被美国食品药品监督管理局（FDA）批准用于临床，但抑郁症的治疗仍需要高效、起效快且副作用少的药物。在本研究中，我们聚焦于降钙素这种胰岛淀粉样多肽，尽管此前已证明降钙素基因相关肽可改善啮齿动物的抑郁样行为，但降钙素的抗抑郁作用尚未见报道。在此，我们首先在慢性应激抑郁小鼠模型中评估了鲑鱼降钙素（sCT）的抗抑郁潜力。我们观察到，在悬尾试验和强迫游泳试验中，慢性应激小鼠的不动时间显著增加。此外，单次给予sCT可成功挽救慢性应激小鼠的抑郁样行为。最后，应用强效胰岛淀粉样多肽受体拮抗剂AC187来研究胰岛淀粉样多肽受体在抑郁症中的作用。我们发现AC187显著消除了sCT的抗抑郁作用。综上所述，我们的数据表明，sCT可能通过胰岛淀粉样多肽信号通路改善抑郁样表型。未来，sCT应被视为抑郁症潜在的治疗候选药物。
