Development of treatment for autism spectrum disorder with exfoliated deciduous tooth-derived pulp stem cells

Research Project

Project/Area Number	17K17334
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Orthodontics/Pediatric dentistry
Research Institution	Kyushu University
Principal Investigator	takayama fumiko 九州大学, 大学病院, 助教 (20795950)
Project Period (FY)	2017-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords	ドパミン神経細胞 / 自閉症 / ミトコンドリア / SHED / 自閉スペクトラム症 / 乳歯歯髄肝細胞 / 視床下部神経細胞 / オキシトシン / 脳神経疾患
Outline of Final Research Achievements	This study aimed to investigate the pathological association between development of dopaminergic neurons (DN) and mitochondria in Autism spectrum disorder (ASD) by using stem cells from human exfoliated deciduous teeth (SHED). The SHED collected from ASD and typically developing children were differentiated into DN, and the neurobiology of these cells was examined. The DN derived from children with ASD showed impaired neurite outgrowth and branching, associated with decreased mitochondrial membrane potential, ATP production, number of mitochondria within the neurites, amount of mitochondria per cell area and intracellular calcium level. In addition, impaired neurite outgrowth and branching of ASD-derived DN were not improved by brain-derived neurotrophic factor (BDNF). Our results suggest that mitochondrial dysfunction caused by impairment of the BDNF signaling pathway reduce dopaminergic neurite outgrowth in ASD.
Academic Significance and Societal Importance of the Research Achievements	ASDは小児の代表的な精神行動異常疾患で、昨今では疾患概念が広範化され約100人に7～8人と推測され、社会問題となっており、一刻も早い病態解明が期待されている。本研究により、ミトコンドリア機能の低下が自閉症の病態発症に関与することが明らかとなり、同疾患の早期治療法の開拓に貢献したと考えられる。