Elucidation of melatonin effects on neurodevelopment of autism spectrum disorder using human deciduous teeth-derived stem cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18785
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57070:Developmental dentistry-related
• Research Institution: Kyushu University
• Principal Investigator: Kifune Takashi 九州大学, 大学病院, 医員 (90830414)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 自閉スペクトラム症 / メラトニン / 神経発達 / 睡眠

Outline of Final Research Achievements

In this study, dental stem cells obtained from children with autism spectrum disorder (ASD) were induced into dopaminergic neurons (ASD-DN), and melatonin effects were analyzed. In the absence of melatonin, ASD-DN showed impaired neurite outgrowth and mitochondrial dysfunction, reduced cytosolic and mitochondrial Ca2+, and Ca2+ accumulation in endoplasmic reticulum (ER), compared to control DN. Melatonin promoted Ca2+ release from ER to mitochondria and improved mitochondrial function and neurite outgrowth. Melatonin also increased cytosolic Ca2+ and promoted dopamine release. Melatonin will be effective in improving development of the dopaminergic system in ASD.

Free Research Field

小児口腔医学

Academic Significance and Societal Importance of the Research Achievements

本研究は、睡眠がメラトニンを介してニューロンの発達をどのように制御するかという観点から、ヒトの脳の発達における睡眠機能の分子機序解明に貢献できる。ニューロンの発達に対するメラトニンの薬理作用を明らかにすることにより、その作用に関連する分子を標的とした睡眠障害の新規治療薬の開発に貢献できる。脳の発達促進という観点から、健常児の睡眠障害に対する生活指導プログラムの構築のために科学的証拠を提示できる。