Molecular mechanisms of exercise-induced hippocampal neurogenesis and antidepressant effects
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DOI[10.31662/jmaj.2023-0010]to the data of the same series
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- Material Type
- 記事
- Author/Editor
- Makoto Kondo
- Publication, Distribution, etc.
- Publication Date
- 2023-04-14
- Publication Date (W3CDTF)
- 2023-04-14
- Periodical title
- JMA Journal
- No. or year of volume/issue
- 6(2)
- Volume
- 6(2)
- ISSN (Periodical Title)
- 2433-3298
- ISSN-L (Periodical Title)
- 2433-328X
- Text Language Code
- eng
- DOI
- 10.31662/jmaj.2023-0010
- Persistent ID (NDL)
- info:ndljp/pid/14494990
- Collection
- Collection (Materials For Handicapped People:1)
- Collection (particular)
- 国立国会図書館デジタルコレクション > 電子書籍・電子雑誌 > その他
- Acquisition Basis
- インターネット資料収集保存事業（WARP）
- Date Accepted (W3CDTF)
- 2025-10-21T09:04:40+09:00
- Date Captured (W3CDTF)
- 2024-09-26
- Format (IMT)
- application/pdf
- Access Restrictions
- インターネット公開
- Availability of remote photoduplication service
- 不可
- Periodical Title (URI)
- Periodical Title (Persistent ID (NDL))
- info:ndljp/pid/14494987
- Data Provider (Database)
- 国立国会図書館 : 国立国会図書館デジタルコレクション
- Summary, etc.
- <p>It is estimated that approximately 280 million people worldwide suffer from depression. Depression is a common disease to us all, and the socioeconomic loss caused by depression is very large. However, there is currently a problem that many depressed patients do not respond to existing antidepressants, including selective serotonin reuptake inhibitors (SSRIs). Therefore, novel and effective therapeutic agents are highly desirable. It has been reported that exercise has preventive effects on depression (antidepressant effects) and that serotonin, whose release increases in the brain with exercise, is involved in exercise-induced antidepressant effects. We focused on the action of serotonin and investigated its role in the antidepressant effect of exercise using gene knockout mice, and then, we found that serotonin type 3 (5-HT3) receptors play an essential role in the antidepressant effect of exercise. We then further investigated the antidepressant effects mediated by 5-HT3 receptors. Our detailed analyses revealed that neurons expressing 5-HT3 receptors are abundant in the subgranular zone of the hippocampal dentate gyrus and produce insulin-like growth factor-1 (IGF-1). In addition, we newly found that the stimulation of 5-HT3 receptors by agonists promotes IGF-1 release in the hippocampus and increases hippocampal neurogenesis via the IGF-1 signaling pathway, resulting in antidepressant effects. Furthermore, we further showed that a 5-HT3 receptor agonist increases hippocampal neurogenesis and exhibits antidepressant effects in mice with depressive-like behavior. A comparison with the effects of existing antidepressant SSRIs revealed that the 5-HT3 receptor-mediated antidepressant action is a new therapeutic mechanism that differs from existing drugs. Our findings suggest a novel 5-HT3 receptor-IGF-1 mechanism, which could lead to the development of new antidepressant drugs for depression based on the molecular mechanism of exercise-induced antidepressant effects and could bring significant benefits to many depressed patients who do not respond to existing drugs such as SSRIs.</p>
- DOI
- 10.31662/jmaj.2023-0010
- Access Restrictions
- インターネット公開
- Data Provider (Database)
- 科学技術振興機構 : J-STAGE
- Summary, etc.
- <p>It is estimated that approximately 280 million people worldwide suffer from depression. Depression is a common disease to us all, and the socioeconomic loss caused by depression is very large. However, there is currently a problem that many depressed patients do not respond to existing antidepressants, including selective serotonin reuptake inhibitors (SSRIs). Therefore, novel and effective therapeutic agents are highly desirable. It has been reported that exercise has preventive effects on depression (antidepressant effects) and that serotonin, whose release increases in the brain with exercise, is involved in exercise-induced antidepressant effects. We focused on the action of serotonin and investigated its role in the antidepressant effect of exercise using gene knockout mice, and then, we found that serotonin type 3 (5-HT3) receptors play an essential role in the antidepressant effect of exercise. We then further investigated the antidepressant effects mediated by 5-HT3 receptors. Our detailed analyses revealed that neurons expressing 5-HT3 receptors are abundant in the subgranular zone of the hippocampal dentate gyrus and produce insulin-like growth factor-1 (IGF-1). In addition, we newly found that the stimulation of 5-HT3 receptors by agonists promotes IGF-1 release in the hippocampus and increases hippocampal neurogenesis via the IGF-1 signaling pathway, resulting in antidepressant effects. Furthermore, we further showed that a 5-HT3 receptor agonist increases hippocampal neurogenesis and exhibits antidepressant effects in mice with depressive-like behavior. A comparison with the effects of existing antidepressant SSRIs revealed that the 5-HT3 receptor-mediated antidepressant action is a new therapeutic mechanism that differs from existing drugs. Our findings suggest a novel 5-HT3 receptor-IGF-1 mechanism, which could lead to the development of new antidepressant drugs for depression based on the molecular mechanism of exercise-induced antidepressant effects and could bring significant benefits to many depressed patients who do not respond to existing drugs such as SSRIs.</p>
- DOI
- 10.31662/jmaj.2023-0010
- Access Restrictions
- インターネット公開
- Related Material (URI)
- Data Provider (Database)
- 国立情報学研究所 : CiNii Research
- Original Data Provider (Database)
- Japan Link Center雑誌記事索引データベースCrossref科学研究費助成事業データベース
- Bibliographic ID (NDL)
- 14494990