Regular exercise and creatine supplementation prevent chronic mild stress-induced decrease in hippocampal...

Area of Science:

• Neuroscience
• Molecular Biology
• Behavioral Science

Background:

• Chronic stress induces depression-like behaviors and reduces hippocampal neurogenesis.
• Exercise and creatine show potential antidepressant effects, but mechanisms are unclear.
• The Wnt/GSK3β/β-catenin pathway is crucial for neurogenesis and mood regulation.

Purpose of the Study:

• To investigate the effects of exercise and creatine on hippocampal neurogenesis and the Wnt/GSK3β/β-catenin pathway in a mouse model of depression.
• To determine if combined exercise and creatine offer synergistic benefits.

Main Methods:

• Mice underwent chronic mild stress, followed by treadmill running and/or creatine supplementation.
• Behavioral tests (TST, FST) assessed depression-like behaviors.
• Immunohistochemistry and Western blot analyzed neurogenesis (Ki-67+, DCX+ cells) and Wnt pathway markers (GSK3β, β-catenin) in the dentate gyrus (DG).
• Wnt signaling was antagonized locally in the DG.

Main Results:

• Exercise and/or creatine reversed stress-induced immobility in behavioral tests.
• Neurogenesis markers (Ki-67+, DCX+) were restored by the treatments.
• GSK3β activity and nuclear β-catenin levels in the DG were modulated by exercise and creatine.
• Wnt pathway antagonism in the DG exacerbated immobility.

Conclusions:

• Combined exercise and creatine significantly improved hippocampal neurogenesis and reversed depression-like behaviors.
• The Wnt/GSK3β/β-catenin pathway is a key mechanism mediating the antidepressant effects of exercise and creatine.
• Synergistic effects of combined treatments were observed.