TNP-ATP is Beneficial for Treatment of Neonatal HypoxiaInduced Hypomyelination and Cognitive Decline  

作　　者：Jie Xiao Yilong Huang Xia Li Longjun Li Ting Yang Lixuan Huang Ling Yang Hong Jiang Hongchun Li Fan Li 

机构地区：[1]Department of Pathology and Pathophysiology, School of Basic Medical Science, Kunming Medical University

出　　处：《Neuroscience Bulletin》2016年第1期99-107,共9页神经科学通报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(81200939 and31260242);National Science and Technology Supporting Plan of China(2014BAI01B00);Natural Science Foundation of Yunnan Province,China(2011FB060);the National Undergraduate Innovation Fund of China(201310678001);the Undergraduate Innovation Fund of Yunnan Province,China(6011202105);Department of Pathology and Pathophysiology, School of Basic Medical Science, Kunming Medical University for his support throughout the study

摘　　要：Our previous study together with other inves- tigations have reported that neonatal hypoxia or ischemia induces long-term cognitive through brain inflammation impairment, at least in part and hypomyelination. How- ever, the detailed mechanisms are not fully understood. Here, we used a rodent model of neonatal hypoxia by subjecting postnatal day 0 （P0） rat pups to systemic hypoxia （3.5 h）. We found that neonatal hypoxia increased the glutamate content and initiated inflammatory responses at 4 h and 1 day after hypoxia, caused hypomyelination in the corpus callosum, and impaired hippocampus-dependent learning and memory when assessed 30-60 days after hypoxia. Interestingly, much of the hypoxia-induced brain damage was ameliorated by treatment with the ATP ana- logue 21,3-0-（2,4,6-trinitrophenyl）-adenosine 5^-triphos- phate （TNP-ATP; blocks all ionotropic P2Xl-7 receptors）, whereas treatment with pyridoxalphosphate-6-azophenyl- 2＇,4＇-disulphonic acid （PPADS; inhibits P2X1-3 and P2X5- 7 receptors） was less neuroprotective. Our data indicated that activation of ionotropic ATP receptors might be par- tially, if not fully, involved in glutamate deregulation, neuroinflammation, hypomyelination, and cognitive dys- function after neonatal hypoxia.Our previous study together with other inves- tigations have reported that neonatal hypoxia or ischemia induces long-term cognitive through brain inflammation impairment, at least in part and hypomyelination. How- ever, the detailed mechanisms are not fully understood. Here, we used a rodent model of neonatal hypoxia by subjecting postnatal day 0 （P0） rat pups to systemic hypoxia （3.5 h）. We found that neonatal hypoxia increased the glutamate content and initiated inflammatory responses at 4 h and 1 day after hypoxia, caused hypomyelination in the corpus callosum, and impaired hippocampus-dependent learning and memory when assessed 30-60 days after hypoxia. Interestingly, much of the hypoxia-induced brain damage was ameliorated by treatment with the ATP ana- logue 21,3-0-（2,4,6-trinitrophenyl）-adenosine 5^-triphos- phate （TNP-ATP; blocks all ionotropic P2Xl-7 receptors）, whereas treatment with pyridoxalphosphate-6-azophenyl- 2＇,4＇-disulphonic acid （PPADS; inhibits P2X1-3 and P2X5- 7 receptors） was less neuroprotective. Our data indicated that activation of ionotropic ATP receptors might be par- tially, if not fully, involved in glutamate deregulation, neuroinflammation, hypomyelination, and cognitive dys- function after neonatal hypoxia.

关 键 词：Neonatal hypoxia. Inflammation. IonotropicATP receptors - Glutamate Memory deficit 

分 类 号：R749.94[医药卫生—神经病学与精神病学]