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

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 recogni tion 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 alleviat e 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 conclusio n, 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.

Source: Journal of Neurochemistry - January 4, 2024 Category: Neuroscience Authors: Bingqing Ding, Jia Lou, Tianqi Qin, Weiwei Xie, Di Li, Peijun Li, Xingyun Wang, Zhenlang Lin, Xiaoling Guo, Jianghu Zhu Tags: ORIGINAL ARTICLE Source Type: research