2. Academic Validation
  3. Chronic salmon calcitonin exerts an antidepressant effect via modulating the p38 MAPK signaling pathway

Chronic salmon calcitonin exerts an antidepressant effect via modulating the p38 MAPK signaling pathway

  • Front Mol Neurosci. 2023 Mar 10:16:1071327. doi: 10.3389/fnmol.2023.1071327.
Wenhui Zhu 1,  Weifen Li 2,  Jian Jiang 1,  Dilong Wang 1,  Xinliang Mao 3,  Jin Zhang 1,  Xunzhi Zhang 4,  Jinlong Chang 1,  Peijia Yao 1,  Xiuyan Yang 1,  Clive Da Costa 5,  Ying Zhang 1,  Jiezhong Yu 6,  Huiliang Li 7 8,  Shupeng Li 2,  Xinjin Chi 1 9,  Ningning Li 1 8 10
Affiliations

Affiliations

  • 1 Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
  • 2 State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China.
  • 3 Perfect Life and Health Institute, Zhongshan, Guangdong, China.
  • 4 College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China.
  • 5 The Francis Crick Institute, London, United Kingdom.
  • 6 The Fourth People's Hospital of Datong City, Datong, China.
  • 7 Wolfson Institute for Biomedical Research, Division of Medicine, Faculty of Medical Sciences, University College London, London, United Kingdom.
  • 8 China-UK Institute for Frontier Science, Shenzhen, China.
  • 9 Department of Anesthesiology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
  • 10 The Fifth People's Hospital of Datong City, Datong, China.
PMID: 36969556 DOI: 10.3389/fnmol.2023.1071327
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.

Keywords

chronic restraint stress; depression; hippocampus; p38/JNK signaling pathway; salmon calcitonin.

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