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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 TypeMulti-year Fund
Research Field Orthodontics/Pediatric dentistry
Research InstitutionKyushu 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。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (1 results)

All 2018

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] Impaired neurite development associated with mitochondrial dysfunction in dopaminergic neurons differentiated from exfoliated deciduous tooth-derived pulp stem cells of children with autism spectrum disorder.2018

    • Author(s)
      Nguyen HTN, Kato H, Masuda K, Yamaza H, Hirofuji Y, Sato H, Phama T, Takayama F, Sakai Y,Ohga S, Taguchi T, Nonaka K
    • Journal Title

      Biochem Biophys Rep

      Volume: 16 Pages: 24-31

    • DOI

      10.1016/j.bbrep.2018.09.004

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research

URL: 

Published: 2017-04-28   Modified: 2020-03-30  

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