子宮内高血糖環境が胎児の脳神経に及ぼす影響

• Published in: 日本薬理学会年会要旨集 p. 3-O-116
• Main Authors: 河原田, 律子, 大上, 桜香, 吉崎, 瞳, 大金, 恵利子, 中村, 彰男, 鳥海, 旭世
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: apoptosis; hyperglycemia; neuron; その他
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.95.0_3-O-116

Introduction: In the neurons of infants born to diabetic mother rats, we found that in utero hyperglycemia promotes excessive advanced glycation endproducts (AGEs). Therefore, our study aimed to elucidate the molecular mechanisms regulating this effect using a neuronal model that mimics the hyperglycemic intrauterine environment.Methods: PC12 cells were cultured in an RPMI medium with 10 mM (control) or 25 mM (high glucose) glucose to investigate the effects of high glucose levels by analysing glycation, reactive oxygen species (ROS), insulin signaling, inflammatory signals, and apoptosis. Results: JNK phosphorylation, ROS, and AGEs were higher and Akt phosphorylation was lower in PC12 cells cultured in the high glucose medium than in cells cultured in the control medium. Furthermore, the high glucose level induced apoptosis by significantly increasing cleaved caspase in PC12 cells in the high glucose medium. Conclusions: In PC12 cells, the excessive AGEs formed inhibited nutrient signaling by increasing inflammatory signaling and induced apoptosis. The results of this cellular model suggest that AGEs, which accumulated in the fetal brain due to intrauterine hyperglycemia, may induce neuronal apoptosis and increase the risk of neurological disorders.