AUTHOR=Zhu Wenhui , Li Weifen , Jiang Jian , Wang Dilong , Mao Xinliang , Zhang Jin , Zhang Xunzhi , Chang Jinlong , Yao Peijia , Yang Xiuyan , Da Costa Clive , Zhang Ying , Yu Jiezhong , Li Huiliang , Li Shupeng , Chi Xinjin , Li Ningning TITLE=Chronic salmon calcitonin exerts an antidepressant effect via modulating the p38 MAPK signaling pathway JOURNAL=Frontiers in Molecular Neuroscience VOLUME=16 YEAR=2023 URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2023.1071327 DOI=10.3389/fnmol.2023.1071327 ISSN=1662-5099 ABSTRACT=

Depression is a common recurrent psychiatric disorder with a high lifetime prevalence and suicide rate. At present, although several traditional clinical drugs such as fluoxetine and ketamine, are widely used, medications with a high efficiency and reduced side effects are of urgent need. Our group has recently reported that a single administration of salmon calcitonin (sCT) could ameliorate a depressive-like phenotype via the amylin signaling pathway in a mouse model established by chronic restraint stress (CRS). However, the molecular mechanism underlying the antidepressant effect needs to be addressed. In this study, we investigated the antidepressant potential of sCT applied chronically and its underlying mechanism. In addition, using transcriptomics, we found the MAPK signaling pathway was upregulated in the hippocampus of CRS-treated mice. Further phosphorylation levels of ERK/p38/JNK kinases were also enhanced, and sCT treatment was able only to downregulate the phosphorylation level of p38/JNK, with phosphorylated ERK level unaffected. Finally, we found that the antidepressant effect of sCT was blocked by p38 agonists rather than JNK agonists. These results provide a mechanistic explanation of the antidepressant effect of sCT, suggesting its potential for treating the depressive disorder in the clinic.