Lu X-J, Chen X-Q, Weng J, Zhang H-Y, Pak D T, Luo J-H, Du J-Z
Division of Neurobiology and Physiology, Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310058, China.
Neuroscience. 2009 Aug 18;162(2):404-14. doi: 10.1016/j.neuroscience.2009.05.011. Epub 2009 May 12.
Spine-associated Rap-specific GTPase-activating protein (SPAR) is a postsynaptic protein that forms a complex with postsynaptic density (PSD)-95 and N-methyl-d-aspartate receptors (NMDARs), and morphologically regulates dendritic spines. Mild intermittent hypoxia (IH, 16.0% O(2), 4 h/day for 4 weeks) is known to markedly enhance spatial learning and memory in postnatal developing mice. Here, we report that this effect is correlated with persistent increases in SPAR expression as well as long-term potentiation (LTP) in the hippocampus of IH-exposed mice. Furthermore, an infusion of SPAR antisense oligonucleotides into the dorsal hippocampus disrupted elevation of SPAR expression, preventing enhanced hippocampal LTP in IH-exposed developing mice and also reducing LTP in normoxic mice, without altering basal synaptic transmission. In SPAR antisense-treated mice, acquisition of the Morris water maze spatial learning task was impaired, as was memory retention in probe trails following training. This study provides the first evidence that SPAR is functionally required for synaptic plasticity and contributes to the IH-induced enhancement of spatial learning and memory in postnatal developing mice.
脊柱相关的Rap特异性GTP酶激活蛋白（SPAR）是一种突触后蛋白，它与突触后致密物（PSD）-95和N-甲基-D-天冬氨酸受体（NMDARs）形成复合物，并在形态上调节树突棘。已知轻度间歇性缺氧（IH，16.0% O₂，每天4小时，持续4周）可显著增强出生后发育中小鼠的空间学习和记忆能力。在此，我们报告这种效应与IH暴露小鼠海马中SPAR表达的持续增加以及长时程增强（LTP）相关。此外，向背侧海马注射SPAR反义寡核苷酸可破坏SPAR表达的升高，阻止IH暴露的发育中小鼠海马LTP的增强，同时也降低常氧小鼠的LTP，而不改变基础突触传递。在SPAR反义处理的小鼠中，Morris水迷宫空间学习任务的获得受损，训练后探测试验中的记忆保持也受损。这项研究提供了首个证据，表明SPAR是突触可塑性功能所必需的，并且有助于出生后发育中小鼠IH诱导的空间学习和记忆增强。
