Neurological Prognostic Prediction in relation with Brain Glycogen Metabolism and Neonatal Asphyxia: Biomarker Discovery and Clinical Application

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10196
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Tokoha University
• Principal Investigator: SUGIE Hideo 常葉大学, 保健医療学部, 教授 (60119980)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 新生児仮死 / 神経後遺症 / 脳性麻痺 / 脳グリコーゲン代謝 / グリコーゲンホスホリラーゼ

Outline of Final Research Achievements

The pathophysiology of neurological sequelae caused by neonatal asphyxia was examined by focusing on brain glycogen metabolism. In 41 cases with a 5-minute Apgar score of 7 or less in term infants, they were classified into a CP group (23 cases) with a neurological sequelae (mainly cerebral palsy) and a TD group with typical development (18 cases), and glycogen phosphorylase ( brain type; PYGB, muscle type; PYGM, liver type; PYGL) gene polymorphism was examined between the two groups. In addition, we also examined phosphofructokinase (muscle type; PFKM, liver type; PFKL, platelet type; PFKP) and phosphorylase kinase, which are glycolytic key enzymes expressed in the brain. Multiple gene variants were found in the target genes, but when compared in the CP group and the TD group, a statistically significant genotype difference was found in PYGL and PFKP (p <0.05).

Free Research Field

小児科学、小児神経学、先天代謝異常症

Academic Significance and Societal Importance of the Research Achievements

脳性麻痺は医療の進歩にも関わらずその発生頻度に顕著な改善はない。未熟児医療の進展に伴って超未熟児の生存予後が改善したことで、皮肉にも重症児の割合が増加している。新生児仮死は周生期の脳損傷の原因の一つで、低酸素、脳虚血による神経細胞の非可逆的損傷を引き起こす。今回満期産新生児仮死におけるCP群とTD群で解糖系酵素遺伝子の一部に有意な遺伝子型の差が認められたことから、これが神経学的予後のリスクを予測する一つのバイオマーカーとなる可能性が考えられる。新生児仮死児で本バリアントを有する個体に対して、早期の医療的介入（リハビリテーションなど）を開始する目安となることが期待できる。