Repetitive transcranial magnetic stimulation and fluoxetine attenuate astroglial activation and benefit behaviours in a chronic unpredictable mild stress mouse model of depression

Abstract

Objectives: Repetitive transcranial magnetic stimulation (rTMS) has been considered as an effective antidepressant treatment; however, the mechanism of its antidepressant effect is still unclear. Fluoxetine, a selective serotonin reuptake inhibitor antidepressant, may be neuroprotective. The objective of the present study was to evaluate the effect and underlying possible neuroprotective mechanism of rTMS and fluoxetine on abnormal behaviours in a depressive mouse model induced by chronic unpredictable mild stress (CUMS).Methods: After 28 days of CUMS exposure, mice were chronically treated with rTMS (10 Hz for 5 s per train, total 20 trains per day) and (or) fluoxetine (5 mg/kg/day, intraperitoneally) for 28 days targeting on the frontal cortex. After the behavioural tests, the protein expressions of glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) were measured by immunohistochemistry and (or) Western Blot.Results: The results showed rTMS and (or) fluoxetine attenuated the locomotion decrease, anxiety and depressive like behaviours in the CUMS-exposed mice.Conclusion: Our results suggest that both rTMS and fluoxetine could benefit the CUMS-induced abnormal behaviours including depressive-like behaviours, and the beneficial effects of rTMS as well as fluoxetine on depression might be partly related to their neuroprotective effect on attenuating astroglial activation and BDNF decrease

Keywords:

• rTMS
• fluoxetine
• astroglia
• GFAP
• BDNF
• depression

Acknowledgments

The authors thank all participants and participating center for their motivated contribution.

Author contributions

Jue He, Wenqiang Wang and Yanlong Liu conceived and designed the research. Qianfa Yuan, Yuying Lei, Kai Yu, Junnan Wu, Chunyan Wen, Zhizhong Xu performed the experiments together. All authors discussed the drafting of the manuscript, and Qianfa Yuan edited the last version of the manuscript.

Ethics statement

The animal study was reviewed and approved by Care and Use of Laboratory Animal Ethics Committee of Xiamen Xian Yue Hospital.

Statement of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Data availability statement

The datasets generated for this study are available on request to the corresponding authors.

Additional information

Funding

This work was supported by grants from Xiamen Medical and Health Guidance Project (3502Z20199092), Fujian Provincial Health Youth Scientific Research Project (2019-2-54), Fujian Provincial Health Commission (2017-CXB-17), and National Nature Science Foundation of China (81871058, 81671266).