TNP-ATP is Beneficial for Treatment of Neonatal Hypoxia-Induced Hypomyelination and Cognitive Decline
TNP-ATP is Beneficial for Treatment of Neonatal Hypoxia-Induced Hypomyelination and Cognitive Decline
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TNP-ATP 有利于治疗新生儿缺氧引起的髓鞘形成低下和认知能力下降
DOI：
10.1007/s12264-015-0003-8
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发表时间：
2016-02-01
影响因子：
5.6
通讯作者：
Li, Fan
中科院分区：
文献类型：
--
作者：
Xiao, Jie;Huang, Yilong;Li, Fan
我们之前的研究与其他研究一起报告了新生儿缺氧或缺血导致长期认知障碍，至少部分是通过脑部炎症和髓鞘减少。然而，其具体机制尚不完全清楚。在这里，我们使用了一种新生缺氧的啮齿动物模型，使出生后第0天(P0)的大鼠幼鼠处于全身缺氧(3.5h)。我们发现，缺氧后4小时和1天，新生儿脑组织谷氨酸含量增加，并引发炎症反应，在缺氧30-60天后评估，可引起胼胝体髓鞘减退，并损害海马区依赖的学习和记忆。有趣的是，用三磷酸腺苷类似物2‘，3’-0-(2，4，6-三硝基苯基)-5‘-三磷酸(TNP-ATP；阻断所有电离型P2X1-7受体)治疗缺氧引起的脑损伤后，大部分脑损伤都得到了改善，而pyridoxalphosphate-6-azophenyl-2′，4′-disulphonic酸(PPADS；抑制P2X1-3和P2X5-7受体)治疗的神经保护作用较弱。我们的数据表明，离子型ATP受体的激活可能部分(如果不是完全)参与了新生儿缺氧后谷氨酸的去调节、神经炎症、髓鞘减少和认知功能障碍。
Our previous study together with other investigations have reported that neonatal hypoxia or ischemia induces long-term cognitive impairment, at least in part through brain inflammation and hypomyelination. However, 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 analogue 2′,3′-0-(2,4,6-trinitrophenyl)-adenosine 5′-triphosphate (TNP-ATP; blocks all ionotropic P2X1-7 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 partially, if not fully, involved in glutamate deregulation, neuroinflammation, hypomyelination, and cognitive dysfunction after neonatal hypoxia.