Expression of VGLUTs contributes to degeneration and acquisition of learning and memory
Expression of VGLUTs contributes to degeneration and acquisition of learning and memory
复制标题
VGLUT 的表达有助于学习和记忆的退化和获得
DOI：
10.1016/j.nlm.2011.01.010
复制
发表时间：
2011-03-01
影响因子：
2.7
通讯作者：
Zhang, Yong-Xiang
中科院分区：
文献类型：
--
作者：
Cheng, Xiao-Rui;Yang, Yong;Zhang, Yong-Xiang
囊泡谷氨酸转运蛋白（VGLUT），包括VGLUT 1、VGLUT 2和VGLUT 3，负责将L-谷氨酸上传到突触囊泡中。VGLUT的表达模式决定了突触囊泡填充的水平（即，谷氨酸量子大小），并直接影响谷氨酸受体和谷氨酸能突触传递;因此，VGLUT可能在中枢神经系统的学习和记忆中发挥关键作用。为了确定VGLUT是否有助于学习和记忆的退化或获得，我们使用了与年龄相关的学习和记忆障碍的动物模型，衰老加速小鼠/易感小鼠8（SAMP 8）。KM小鼠根据其在穿梭箱测试中的学习和记忆表现分组。采用实时荧光定量PCR和western blot方法分别检测大脑皮层和海马VGLUTs和突触素（Syp）mRNA和蛋白的表达。我们的研究结果表明，在大脑皮层中，VGLUT 1，VGLUT 2，VGLUT 3和Syp的蛋白表达随着年龄的增长而下降，在KM小鼠中增加，这显示出学习和记忆能力的增强。SAMP 8海马VGLUT 2和Syp蛋白表达随增龄而降低。VGLUT 1和VGLUT 2蛋白表达水平在KM小鼠组中最高，在穿梭箱试验中具有76-100%的回避评分。这些数据表明，VGLUT 1，VGLUT 2和Syp的蛋白质表达在SAMP 8中以年龄依赖性方式降低，并在KM小鼠中以学习和记忆依赖性方式增加。相关性分析表明VGLUT 1、VGLUT 2和Syp蛋白表达与学习记忆能力呈正相关。(C)2011 Elsevier Inc. All rights reserved.
Vesicular glutamate transporters (VGLUTs), which include VGLUT1, VGLUT2 and VGLUT3, are responsible for the uploading of L-glutamate into synaptic vesicles. The expression pattern of VGLUTs determines the level of synaptic vesicle filling (i.e., glutamate quantal size) and directly influences glutamate receptors and glutamatergic synaptic transmission; thus, VGLUTs may play a key role in learning and memory in the central nervous system. To determine whether VGLUTs contribute to the degeneration or acquisition of learning and memory, we used an animal model for the age-related impairment of learning and memory, senescence-accelerated mouse/prone 8 (SAMP8). KM mice were divided into groups based on their learning and memory performance in a shuttle-box test. The expression of VGLUTs and synaptophysin (Syp) mRNA and protein in the cerebral cortex and hippocampus were investigated with real-time fluorescence quantitative PCR and western blot, respectively. Our results demonstrate that, in the cerebral cortex, protein expression of VGLUT1, VGLUT2, VGLUT3 and Syp was decreased in SAMP8 with age and increased in KM mice, which displayed an enhanced capacity for learning and memory. The protein expression of VGLUT2 and Syp was decreased in the hippocampus of SAMP8 with aging. The expression level of VGLUT1 and VGLUT2 proteins were highest in KM mouse group with a 76-100% avoidance score in the shuttle-box test. These data demonstrate that protein expression of VGLUT1, VGLUT2 and Syp decreases age-dependently in SAMP8 and increases in a learning- and memory-dependent manner in KM mice. Correlation analysis indicated the protein expression of VGLUT1, VGLUT2 and Syp has a positive correlation with the capacity of learning and memory. (C) 2011 Elsevier Inc. All rights reserved.