ASK1 promotes uterine inflammation leading to pathological periventricular leukomalacia

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K22757
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Yoshikawa Midori 東京大学, 医学部附属病院, 届出研究員 (90881441)
• Project Period (FY): 2020-09-11 – 2023-03-31
• Keywords: ASK1 / PVL / LPS

Outline of Final Research Achievements

A PVL model has already been established in which LPS administration to pregnant mice induces white matter damage, typified by oligodendrocyte damage, in fetuses and neonates.① ASK1-/- （female）× ASK1+/- （male）→half the number of fetus:ASK1+/- , half the number of fetus:ASK1-/-　② ASK1+/+ （female）× ASK1+/- （male）→half the number of fetus:ASK1+/+ 、half the number of fetus:ASK1+/-　③ ASK1+/- （female）× ASK1+/- （male）→half the number of fetus:ASK1+/-、quarter of fetus:ASK1+/+, ASK1-/-
A PVL model was performed for each of the 3 groups by the mating method of 3 types of KO mice, but it has not yet been reproduced.

Free Research Field

周産期

Academic Significance and Societal Importance of the Research Achievements

脳性麻痺は胎児期の発達する脳が侵襲を受け, 重篤な神経学的後遺症をきたす運動機能障害である。脳性麻痺児の約半数以上を早産児が占め, 早産児の脳性麻痺の主要な原因は脳室周囲白質軟化症(Periventricular leukomalacia; PVL)である。PVLは子宮内感染による過剰な炎症の脳への波及や低酸素虚血による病的ストレスが原因とされる。いまだにPVLに対する根本的な治療法はない。本研究でApoptosis signal-regulating kinase1 （ASK1）が子宮内感染に伴う過剰な炎症を惹起し、PVL発症に関与することが明らかとできれば、今後新たな治療法となりうる。