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The 5-HT3 receptor is essential for exercise-induced hippocampal neurogenesis and antidepressant effects

Molecular Psychiatry volume 20, pages 1428–1437 (2015)Cite this article

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Abstract

Exercise has a variety of beneficial effects on brain structure and function, such as hippocampal neurogenesis, mood and memory. Previous studies have shown that exercise enhances hippocampal neurogenesis, induces antidepressant effects and improves learning behavior. Brain serotonin (5-hydroxytryptamine, 5-HT) levels increase following exercise, and the 5-HT system has been suggested to have an important role in these exercise-induced neuronal effects. However, the precise mechanism remains unclear. In this study, analysis of the 5-HT type 3A receptor subunit-deficient (htr3a−/−) mice revealed that lack of the 5-HT type 3 (5-HT3) receptor resulted in loss of exercise-induced hippocampal neurogenesis and antidepressant effects, but not of learning enhancement. Furthermore, stimulation of the 5-HT3 receptor promoted neurogenesis. These findings demonstrate that the 5-HT3 receptor is the critical target of 5-HT action in the brain following exercise, and is indispensable for hippocampal neurogenesis and antidepressant effects induced by exercise. This is the first report of a pivotal 5-HT receptor subtype that has a fundamental role in exercise-induced morphological changes and psychological effects.

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Acknowledgements

This work was supported by JSPS KAKENHI grant number 26860926, and grants from the Uehara Memorial Foundation, the Japan Prize Foundation, Brain Science Foundation, the Sakamoto Research Foundation of Psychiatric Diseases, Takeda Science Foundation, the Ichiro Kanehara Foundation, Kanae Foundation, Suzuken Memorial Foundation and Meiji Yasuda Life Foundation. We thank Shingo Miyata (Kinki University) for technical assistance.

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  1. Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Suita, Japan

    M Kondo, Y Nakamura, Y Ishida & S Shimada

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Kondo, M., Nakamura, Y., Ishida, Y. et al. The 5-HT3 receptor is essential for exercise-induced hippocampal neurogenesis and antidepressant effects. Mol Psychiatry 20, 1428–1437 (2015). https://doi.org/10.1038/mp.2014.153

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