Hippocampal spine-associated Rap-specific GTPase-activating protein induces enhancement of learning and memory in postnatally hypoxia-exposed mice.
Hippocampal spine-associated Rap-specific GTPase-activating protein induces enhancement of learning and memory in postnatally hypoxia-exposed mice.
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DOI：
10.1016/j.neuroscience.2009.05.011
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发表时间：
2009-08-18
期刊：
影响因子：
3.3
通讯作者：
Du, J. -Z.
中科院分区：
文献类型：
--
作者：
Lu, X. -J.;Chen, X. -Q.;Weng, J.;Zhang, H. -Y.;Pak, D. T.;Luo, J. -H.;Du, J. -Z.
Spine-associated Rap-specific GTPase-activating protein（SPAR）是一种突触后蛋白，与突触后密度（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。轻度间歇性低氧（IH，16.0%O2，4 h/d，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。在这里，我们报告说，这种效果与持续增加SPAR表达以及长时程增强（LTP）在IH暴露小鼠海马。此外，注入SPAR反义寡核苷酸到背侧海马破坏SPAR表达的升高，防止IH暴露的发育中小鼠的海马LTP增强，也减少了常氧小鼠的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，训练后在探测路径中的记忆保持也受损。本研究提供了第一个证据表明，SPAR是突触可塑性的功能所需的，并有助于IH诱导的增强出生后发育中的小鼠的空间学习和记忆。
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% O2, 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.
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影响因子：
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