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2016 Fiscal Year Final Research Report

Mechanisms of mitochondrial DNA release in the CNS

Research Project

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Project/Area Number 15H06372
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionOsaka University

Principal Investigator

Sakakibara Kaori  大阪大学, 医学系研究科, 特任研究員 (40621280)

Co-Investigator(Renkei-kenkyūsha) Okuno Tatsusada  大阪大学医学系研究科, 助教 (00464248)
Project Period (FY) 2015-08-28 – 2017-03-31
KeywordsミトコンドリアDNA / 視神経脊髄炎 / 自然免疫
Outline of Final Research Achievements

Mitochondrial DNA (mtDNA),one of damage-associated molecular patterns, has been reported to stimulate innate immunity. Recent studies suggest that activation of innate immunity occurs in the acute phase of NMOSD. We measured mtDNA levels in cerebrospinal fluid of NMOSD and compared to these of multiple sclerosis and other neurological diseases (ONDs) using quantitative PCR. We stimulated mouse primary astrocyte cultures with AQP4-Ab and measured the level of mtDNA in the supernatant. We added DNA fraction from the culture supernatant to microglia cultures, and measured IL-1β in the supernatants. The level of mtDNA was significantly higher in patients with acute NMOSD than remission NMOSD, acute MS, and ONDs. mtDNA level was increased in the supernatant of astrocyte cultures stimulated with AQP4-Ab. We also demonstrated that mtDNA promoted IL-1β secretion from microglia.
AQP4-Ab promotes mtDNA release from astrocytes. Our results suggests that mtDNA might be involved in NMOSD pathogen

Free Research Field

神経免疫学

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Published: 2018-03-22  

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