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2023 Fiscal Year Final Research Report

Functional analysis of serotonergic innervation using a visualisation model to challenge paediatric intestinal peristalsis

Research Project

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Project/Area Number 18K08554
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionOsaka Medical and Pharmaceutical University

Principal Investigator

Tomiyama Hideki  大阪医科薬科大学, 医学部, 准教授 (20298433)

Co-Investigator(Kenkyū-buntansha) 谷口 高平  大阪医科薬科大学, 医学部, 講師 (70779686)
内山 和久  大阪医科薬科大学, 医学部, 名誉教授 (80232867)
Project Period (FY) 2018-04-01 – 2024-03-31
Keywordsゼブラフィッシュ / 腸管神経系 / 蠕動 / セロトニン
Outline of Final Research Achievements

To elucidate the serotonergic neuronal functions within the enteric nervous system and the pathophysiology of intestinal dysmotility, we have established an experimental model using zebrafish, which remain transparent during development and differentiation, allowing for internal observation. Analysis of intestinal motility using the SONY SI8000 Cell Motion System revealed that antegrade and retrograde peristalsis are formed with distinct contraction vectors. Moreover, we discovered that the hcn4 gene, which is expressed in cardiac pacemaker cells, regulates retrograde peristalsis. Additionally, we successfully developed an hcn4 gene knockout model and observed a reduction in retrograde peristalsis.

Free Research Field

小児蠕動機能不全症

Academic Significance and Societal Importance of the Research Achievements

ヒルシュプルング病や腸管神経節細胞僅少症などに代表される腸管蠕動不全症は希少疾患であり、癌研究などと比較して研究が遅れている分野である。その克服のためには可能な限り実際の生体内を模倣した良質な実験系モデルが必要である。よってゲノム編集が容易で、胎生変化に加え、透明で全腸の観察が生きた同一個体内で可能なゼブラフィッシュモデルが最適であると考え研究に着手した。神経発生に関与するセロトニン神経の機能を本モデルで解析することは、胎生期に腸管神経系の発達異常をきたす疾患の病態解明に繋がる。

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Published: 2025-01-30  

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