The 5-HT3 receptor is essential for exercise-induced hippocampal neurogenesis and antidepressant effects.
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.
Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Suita, Japan.
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M
Kondo
Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Suita, Japan.
Y
Y
Nakamura
Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Suita, Japan.
Y
Y
Ishida
Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Suita, Japan.
S
S
Shimada
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D000089622:Doublecortin Domain Proteins; D005106:Exploratory Behavior / Q000187:drug effects; D005239:Fear / Q000187:drug effects / Q000523:psychology; D019417:Hindlimb Suspension; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology; D013550:Swimming / Q000523:psychology
D000928:Antidepressive Agents; D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010880:Piperidines; D044406:Receptors, Serotonin, 5-HT3; D018490:Serotonin Agents; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine; C083009:4-amino-1-(6-chloro-2-pyridyl)piperidine hydrochloride