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

2018 Fiscal Year Final Research Report

• 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
• Keywords: ドパミン神経細胞 / 自閉症 / ミトコンドリア / SHED

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.

Free Research Field

小児歯科学

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。