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

Yea-Hyun Leem, Morimasa Kato, Hyukki Chang

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    Regular exercise and creatine supplementation reversed depression-like behaviors in mice by enhancing hippocampal neurogenesis. This occurred through the activation of the Wnt/GSK3β/β-catenin pathway in the dentate gyrus.

    Keywords:
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    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.