1. Academic Validation
  2. Significance of gastrointestinal tract in the therapeutic mechanisms of exercise in depression: Synchronism between brain and intestine through GBA

Significance of gastrointestinal tract in the therapeutic mechanisms of exercise in depression: Synchronism between brain and intestine through GBA

  • Prog Neuropsychopharmacol Biol Psychiatry. 2020 Dec 20;103:109971. doi: 10.1016/j.pnpbp.2020.109971.
Yanna Liu 1 Fenghua Xu 2 Shuang Liu 1 Gang Liu 3 Xiaohan Yang 3 Wenting Gao 4 Kai Fan 1 Henan Zhao 5 Jianmei Ma 6
Affiliations

Affiliations

  • 1 Department of Anatomy, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China.
  • 2 Department of Anatomy, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China; Department of Gastroenterology, Army Medical Center of PLA affiliated with Army Medical University, Chongqing, China.
  • 3 National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian, Liaoning, China.
  • 4 Institute of Genetically Engineered Animal Models for Human Diseases, Dalian Medical University, Dalian, Liaoning, China.
  • 5 Department of Pathophysiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China.
  • 6 Department of Anatomy, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China; National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian, Liaoning, China. Electronic address: ma_jianmei@hotmail.com.
Abstract

Researchers have made considerable progress in elucidating psychological and exercise correlates of major depressive disorder (MDD). However, as the largest immune organ, far less is known about the role of gastrointestinal (GI) tract in the therapeutic mechanisms of exercise in MDD. In addition to the sites of the digestive tract that absorb nutrients, the GI tract also serves as a protective barrier against organisms. Inflammation and other consequences caused by disrupted GI barrier integrity are considered to be one of the mechanisms of depression, and the gut-brain axis (GBA) plays a critical role in this process. In this work, we observed the depression-like behaviors, intestinal barrier, central and peripheral inflammation, and related neurotransmitters through exercise intervention in the chronic unpredictable mild stress (CUMS) model, aiming to clarify the mechanisms of exercise to improve depression through GBA. Our results revealed that, following increased expressions of pro-inflammatory factors in intestine of CUMS mice, the levels of pro-inflammatory factors were all significantly raised in serum and brain simultaneously. Further, glial cells were activated in visceral nervous system and its related brain regions at the same time, accompanied by lower expression of occludin in CUMS mice. Importantly, our findings provide the first evidence that eight weeks of running exercise effectively inhibited neuro-immune interactions along gut-brain-axis and contributed obvious improvement of intestinal epithelial barrier (IEB). Finally, multivariate analysis putatively highlighted the role of exercise-induced IEB protection on depression treatment. We hope that our findings could warrant further study of therapeutic mechanisms of exercise in depression, specifically in disentangling the roles of intestinal function and IEB protection, and for developing more targeted clinical depression interventions.

Keywords

Depression; Exercise; Gut–brain axis (GBA); Intestinal epithelial barrier (IEB); Multivariate analysis.

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