神经酰胺
愤怒(情绪)
莫里斯水上航行任务
败血症
药理学
医学
细胞凋亡
生物
海马体
免疫学
内分泌学
神经科学
生物化学
作者
Lina Zhang,Yuan Jiang,Songyun Deng,Yunan Mo,Yan Huang,Wenchao Li,Chenglong Ge,Xinshu Ren,Haisong Zhang,Xiaolei Zhang,Qianyi Peng,Zhiyong Liu,Li Huang,Fan Zhou,Yuhang Ai
出处
期刊:Life Sciences
[Elsevier]
日期:2021-07-01
卷期号:277: 119490-119490
被引量:13
标识
DOI:10.1016/j.lfs.2021.119490
摘要
Sepsis-associated encephalopathy (SAE) is one of the most common complications of sepsis, and it might lead to long-term cognitive dysfunction and disability. This study aimed to explore the role of S100 calcium binding protein B (S100B)/RAGE/ceramide signaling pathway in SAE. FPS-ZM1 (an inhibitor of RAGE), myriocin and GW4869 (an inhibitor of ceramide) were used to explore the role of S100B/RAGE/ceramide in acute brain injury and long-term cognitive impairment in sepsis. In addition, Mdivi-1 (inhibitor of Drp1) and Drp1 siRNA were utilized to assess the effects of C2-ceramide on neuronal mitochondria, and to explore the specific underlying mechanism in C2 ceramide-induced death of HT22 mouse hippocampal neuronal cells. Western blot analysis showed that sepsis significantly up-regulated S100B and RAGE. Nissl staining and Morris water maze (MWM) test revealed that inhibition of RAGE with FPS-ZM1 markedly attenuated cecal ligation and puncture (CLP)-induced brain damage and cognitive dysfunction. Furthermore, FPS-ZM1 relieved sepsis-induced C2-ceramide accumulation and abnormal mitochondrial dynamics. Moreover, inhibition of ceramide also showed similar protective effects both in vivo and in vitro. Furthermore, Mdivi-1 and Drp1 siRNA significantly reduced C2-ceramide-induced neuronal mitochondrial fragmentation and cell apoptosis in vitro. This study confirmed that S100B regulates mitochondrial dynamics through RAGE/ceramide pathway, in addition to the role of this pathway in acute brain injury and long-term cognitive impairment during sepsis.
科研通智能强力驱动
Strongly Powered by AbleSci AI