Role of the 5-HT4 receptor in neurogenic activity of chronic fluoxetine in the dentate gyrus and its association with mature granule cell dematuration

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460096
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Tokyo University of Science (2015); Kyoto University (2013-2014)
• Principal Investigator: SEGI ERI 東京理科大学, 基礎工学部, 准教授 (70378628)
• Co-Investigator(Renkei-kenkyūsha): KOBAYASHI KATSUNORI 日本医科大学, 医学部, 准教授 (10322041)
• Research Collaborator: IMOTO YUKI
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 海馬 / 抗うつ薬 / 神経神経 / セロトニン受容体

Outline of Final Research Achievements

Chronic treatment with selective serotonin (5-HT) reuptake inhibitors (SSRIs) facilitates adult neurogenesis in the dentate gyrus (DG) of the hippocampus. However, it is largely unknown how the 5-HT4 receptor mediates neurogenic effects in the DG. I addressed this issue using 5-HT4 receptor knockout (5-HT4R KO) mice. Expression of the 5-HT4 receptor was detected in mature GCs but not in neuronal progenitors of the DG. Chronic treatment with the SSRI fluoxetine significantly increased cell proliferation and the number of doublecortin-positive cells in the DG of wild-type mice, but not in 5-HT4R KO mice. I also demonstrated that fluoxetine-induced adult neurogenesis and granule cell dematuration are closely associated, providing new insight into the cellular mechanisms of the neurogenic actions of SSRIs in the hippocampus.

Free Research Field

医歯薬学