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Adult Neurogenesis

開催日 2014/9/12
時間 17:10 - 18:10
会場 Room J(313+314)
Chairperson(s) 影山 龍一郎 / Ryoichiro Kageyama (京都大学ウイルス研究所 / Institute for Virus Research, Kyoto University, Japan)
金子 奈穂子 / Naoko Kaneko (名古屋市立大学大学院医学研究科 再生医学分野 / Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Japan)

抗うつ薬SSRI投与による海馬歯状回の 神経新生促進作用における5-HT4受容体の役割
The role of 5-HT4 receptor in neurogenic action by chronic fluoxetine in dentate gyrus of mouse hippocampus

  • O2-J-5-4
  • 井本 有基 / Yuki Imoto:1 西谷 直也 / Naoya Nishitani:2 永安 一樹 / Kazuki Nagayasu:2 中川 貴之 / Takayuki Nakagawa:2 金子 周司 / Shuji Kaneko:2 小林 克典 / Katsunori Kobayashi:3,4 瀬木(西田) 恵里 / Eri Segi-Nishida:5 
  • 1:京都大院・薬・生体情報制御 / Dept. Physiol. Chem., Kyoto Univ. Pharm. Sci., Japan 2:京都大院・薬・生体機能解析 / Dept. Mol. Pharm., Kyoto Univ. Pharm. Sci., Japan 3:日本医科大院・医・薬理 / Dept. Pharmacol., Nippon Med. Sch., Japan 4:科学技術振興機構・CREST / JST,CREST, Japan 5:京都大院・薬・統合薬学教育開発センター / Cntr Integrat. Edu in Pharm. And Pharm. Sci. Kyoto Univ., Japan 

Chronic treatment of selective serotonin (5-HT) reuptake inhibitors (SSRIs) including fluoxetine increases adult neurogenesis in the dentate gyrus (DG) of the hippocampus. Among 14 subtypes of 5-HT receptors, pharmacological effects of 5-HT4 receptor (5-HT4R) on antidepressant-like behaviors and neurogenic actions of the DG have been suggested. However, the contribution of 5-HT4R signaling to the enhanced adult neurogenesis by chronic SSRI treatment has not fully understood. Using 5-HT4R deficient (5-HT4R KO) mice of C57BL/6-background, we found that the 5-HT4R plays an important role in the neurogenesis enhanced by chronic fluoxetine treatment in the DG. The chronic fluoxetine treatment significantly increased the cell proliferation and the number of immature neurons in the DG of wild-type mice, while no significant change was observed in the DG of 5-HT4R KO mice. In contrast, after an injection of fluoxetine, basal 5-HT content and extracellular 5-HT accumulation in the hippocampus were not different between wild-type and 5-HT4R KO mice. The expression of 5-HT4Rs in the DG were mainly detected in mature granule neurons, but not in proliferating cells, suggesting that the 5-HT4R in mature granule neurons mediates proliferating signals to neural progenitor cells. These results suggest the importance of 5-HT4R in the responses of chronic fluoxetine treatment in the DG. Our results lead to a molecular understanding of the enhanced serotonergic signaling in the regulatory mechanism of the adult neurogenesis.

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