Neuroplastin 65 mediates cognitive functions via excitatory/inhibitory synapse imbalance and ERK signal pathway
Neuroplastin 65 mediates cognitive functions via excitatory/inhibitory synapse imbalance and ERK signal pathway
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Neuroplastin 65 通过兴奋/抑制性突触失衡和 ERK 信号通路介导认知功能
DOI：
10.1016/j.nlm.2015.11.020
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发表时间：
2016-01-01
影响因子：
2.7
通讯作者：
Yuan, Qionglan
中科院分区：
文献类型：
--
作者：
Amuti, Siyiti;Tang, Yuchun;Yuan, Qionglan
神经致活素65（Neuroplastin 65，NP 65）是突触膜的脑特异性糖蛋白组分，其主要位于前脑如皮质、杏仁核和纹状体以及海马中。先前的研究表明，NP 65与突触可塑性有关，因此推测其在认知功能中发挥作用。为了验证这一假设，我们制备了NP 65基因敲除（KO）小鼠，并发现敲除小鼠表现出增强的海马依赖性学习和记忆，如Morris水迷宫测试和避暗被动回避测试所示，但表现出焦虑样行为，如旷场测试和光/暗探索测试所示。此外，分子和细胞研究揭示了几种改变，包括：（1）兴奋性突触与抑制性突触的比例增加;（2）NMDA受体NR 2A的表达增加;（3）ERK信号转导的激活增强;（4）NP 65 KO小鼠中蘑菇形和分叉形树突棘的数量减少。总之，我们的研究结果表明，NP 65可能介导认知功能。(C)2015 Elsevier Inc. All rights reserved.
Neuroplastin 65 (NP65) is a brain-specific glycoprotein component of synaptic membrane, which is predominantly located in the forebrain such as the cortex, amygdala and striatum and hippocampus. Previous studies have shown that NP65 is implicated in synaptic plasticity, so it was hypothesized to play roles in cognitive functions. To test this hypothesis, we generated NP65 knock-out (KO) mice and found that the null mice exhibited enhanced hippocampus-dependent learning and memory as manifested by Morris water maze test and step-through passive avoidance test, but showed anxiety-like behaviors as manifested by open field test and light/dark exploration test. In addition, molecular and cellular studies revealed several alterations including: (1) the enhanced ratio of excitatory to inhibitory synapses; (2) increased expression of NMDA receptors NR2A; (3) enhanced activation of ERK signaling; (4) lowered number of the mushroom- and bifurcate-shaped dendritic spines in NP65 KO mice. Together, our findings suggest that NP65 may mediate cognitive functions. (C) 2015 Elsevier Inc. All rights reserved.