L‐ascorbyl‐2‐phosphate alleviates white matter injury caused by chronic hypoxia through the PRMT5/P53/NF‐κB pathway

• Published in: Journal of neurochemistry Vol. 168; no. 2; pp. 142 - 160
• Main Authors: Ding, Bingqing, Lou, Jia, Qin, Tianqi, Xie, Weiwei, Li, Di, Li, Peijun, Wang, Xingyun, Lin, Zhenlang, Guo, Xiaoling, Zhu, Jianghu
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.02.2024
• Subjects: Abnormalities; Animals; Animals, Newborn; Ascorbic acid; Ascorbic Acid - metabolism; Brain Injuries - pathology; Complications; Electron microscopy; Flow cytometry; Hypoxia; Hypoxia - metabolism; Immunofluorescence; Immunohistochemistry; In vivo methods and tests; inflammation; Injuries; Mice; Motor skill learning; Myelin; NF-kappa B - metabolism; Object recognition; Olig2 protein; oligodendrocyte; Oligodendrocytes; Oxygen - metabolism; p53 Protein; Pathogenesis; Pattern recognition; Polymerase chain reaction; Premature birth; Protein arginine methyltransferase; Sheaths; Substantia alba; Tumor Suppressor Protein p53 - metabolism; vitamin C; Western blotting; White Matter - pathology; white matter injury; hypoxia; inflammation; vitamin C; white matter injury; oligodendrocyte
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.16038

White matter injury (WMI) is one of the most serious complications associated with preterm births. Damage to oligodendrocytes, which are the key cells involved in WMI pathogenesis, can directly lead to myelin abnormalities. L‐ascorbyl‐2‐phosphate (AS‐2P) is a stable form of vitamin C. This study aimed to explore the protective effects of AS‐2P against chronic hypoxia‐induced WMI, and elucidate the underlying mechanisms. An in vivo chronic hypoxia model and in vitro oxygen–glucose deprivation (OGD) model were established to explore the effects of AS‐2P on WMI using immunofluorescence, immunohistochemistry, western blotting, real‐time quantitative polymerase chain reaction, Morris water maze test, novel object recognition test, beaming‐walking test, electron microscopy, and flow cytometry. The results showed that AS‐2P resulted in the increased expression of MBP, Olig2, PDGFRα and CC1, improved thickness and density of the myelin sheath, and reduced TNF‐α expression and microglial cell infiltration to alleviate inflammation in the brain after chronic hypoxia. Moreover, AS‐2P improved the memory, learning and motor abilities of the mice with WMI. These protective effects of AS‐2P may involve the upregulation of protein arginine methyltransferase 5 (PRMT5) and downregulation of P53 and NF‐κB. In conclusion, our study demonstrated that AS‐2P attenuated chronic hypoxia‐induced WMI in vivo and OGD‐induced oligodendrocyte injury in vitro possibly by regulating the PRMT5/P53/NF‐κB pathway, suggesting that AS‐2P may be a potential therapeutic option for WMI. Our study demonstrated that AS‐2P could attenuate chronic hypoxia‐induced WMI in vivo and OGD‐induced oligodendrocyte injury in vitro through possible regulation of the PRMT5/P53/NF‐κB pathway, which suggested that AS‐2P may be a potential therapeutic option for WMI. Abbreviations: AS‐2P, L‐ascorbyl‐2‐phosphate; OGD, oxygen–glucose deprivation; and WMI, white matter injury.