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Updated: Jun 12, 2025
Animal Models of Depression - Chronic Despair Model CDM
Published on: September 23, 2021
Running exercise decreases microglial activation in the medial prefrontal cortex in an animal model of depression
Shan Liu1, Qian Xiao2, Jing Tang1
1Laboratory of Stem Cells and Tissue Engineering, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, People's Republic of China; Department of Histology and Embryology, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, People's Republic of China.
Background:
Running exercise effectively ameliorates depressive symptoms in humans and depression-like behaviors in animals, but the underlying mechanisms remain unclear. Microglia-mediated neuroinflammation plays a major role in the development of depression. The medial prefrontal cortex (mPFC) is a key brain region involved in depression and is sensitive to physical activity. Whether the antidepressant effect of running exercise involves changes in mPFC microglia is not understood.
Methods:
The animals were subjected to chronic unpredictable stress (CUS) intervention followed by treadmill running. The sucrose preference test and elevated plus maze test or tail suspension test were used for behavioral assessment of the animals. The number of microglia in the mPFC was quantified by immunohistochemistry and stereology. The density and morphology of microglia were analyzed via immunofluorescence staining combined with three-dimensional laser scanning techniques. The mRNA expressions of inflammatory cytokines in the mPFC were examined via quantitative real-time PCR.
Results:
Running exercise effectively alleviated depressive-like behaviors in depression model animals. Running exercise reversed the increase in the number of microglia and the density of activated microglia in the mPFC of CUS animals. Running exercise effectively reversed the changes in microglia (reduced cell body area, total branch length and branch complexity) in the mPFC of CUS animals. Furthermore, running exercise regulated the gene expressions of pro-/antiinflammatory cytokines in the mPFC of CUS animals.
Conclusions:
Our results suggested that the antidepressant effects of running exercise may involve decreasing the number of activated microglia, reversing morphological changes in microglia in the mPFC, and reducing inflammatory responses.
Insights
Running exercise alleviates depression by reducing activated microglia and inflammation in the medial prefrontal cortex (mPFC). This study clarifies how physical activity impacts brain cells to combat depression-like behaviors.
Area of Science:
- Neuroscience
- Exercise Physiology
- Psychiatry
Background:
- Depression is linked to neuroinflammation, particularly involving microglia.
- The medial prefrontal cortex (mPFC) is crucial in depression and affected by exercise.
- Mechanisms of exercise's antidepressant effects, especially concerning mPFC microglia, are unclear.
Purpose of the Study:
- To investigate if running exercise alters microglia in the mPFC of depression model animals.
- To understand the role of mPFC microglia in the antidepressant effects of running exercise.
Main Methods:
- Animals underwent chronic unpredictable stress (CUS) followed by treadmill running.
- Behavioral tests (sucrose preference, elevated plus maze, tail suspension) assessed depression-like behaviors.
- mPFC microglia were quantified (number, density, morphology) and inflammatory cytokine gene expression was analyzed.
Main Results:
- Running exercise improved depression-like behaviors in CUS animals.
- Exercise reversed increased microglia numbers and activation density in the mPFC.
- Exercise normalized microglia morphology and regulated pro-/anti-inflammatory cytokine gene expression in the mPFC.
Conclusions:
- Running exercise exerts antidepressant effects partly by modulating mPFC microglia.
- Exercise reduces the number of activated microglia and normalizes their morphology.
- Exercise decreases neuroinflammation in the mPFC, contributing to its antidepressant action.
