| 查看: 166 | 回复: 0 | |||
| 当前主题已经存档。 | |||
轩辕之客金虫 (小有名气)
|
[交流]
Nature :早衰蛋白控制神经传输物质的释放
|
||
|
Nature 460, 632-636 (30 July 2009) | doi:10.1038/nature08177 Presenilins are essential for regulating neurotransmitter release Chen Zhang1,2, Bei Wu1, Vassilios Beglopoulos1, Mary Wines-Samuelson1, Dawei Zhang1, Ioannis Dragatsis3, Thomas C. Südhof2 & Jie Shen1 1 Center for Neurologic Diseases, Brigham & Women's Hospital, Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA 2 Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Palo Alto, California 94304, USA 3 Department of Physiology, The University of Tennessee, Health Science Center, Memphis, Tennessee 38163, USA Mutations in the presenilin genes are the main cause of familial Alzheimer's disease. Loss of presenilin activity and/or accumulation of amyloid-peptides have been proposed to mediate the pathogenesis of Alzheimer's disease by impairing synaptic function1, 2, 3, 4, 5. However, the precise site and nature of the synaptic dysfunction remain unknown. Here we use a genetic approach to inactivate presenilins conditionally in either presynaptic (CA3) or postsynaptic (CA1) neurons of the hippocampal Schaeffer-collateral pathway. We show that long-term potentiation induced by theta-burst stimulation is decreased after presynaptic but not postsynaptic deletion of presenilins. Moreover, we found that presynaptic but not postsynaptic inactivation of presenilins alters short-term plasticity and synaptic facilitation. The probability of evoked glutamate release, measured with the open-channel NMDA (N-methyl-d-aspartate) receptor antagonist MK-801, is reduced by presynaptic inactivation of presenilins. Notably, depletion of endoplasmic reticulum Ca2+ stores by thapsigargin, or blockade of Ca2+ release from these stores by ryanodine receptor inhibitors, mimics and occludes the effects of presynaptic presenilin inactivation. Collectively, these results indicate a selective role for presenilins in the activity-dependent regulation of neurotransmitter release and long-term potentiation induction by modulation of intracellular Ca2+ release in presynaptic terminals, and further suggest that presynaptic dysfunction might be an early pathogenic event leading to dementia and neurodegeneration in Alzheimer's disease. 原文下载：http://d.namipan.com/d/dfaf22de7 ... de06f1a110a079d1700 http://d.namipan.com/d/dfaf22de7391812fe751559102045de06f1a110a079d1700 |
回复此楼» 猜你喜欢
欢迎发来filecode的Mz6后的代码验证其规律
已经有59人回复
-
filecode=后面第一个是大写字母
已经有5人回复
-
时间戳又变了8-15
已经有21人回复
-
有时候，自然基金真的不能太认真 （我的申报经验）
已经有10人回复
-
filecode
已经有12人回复
-
小木虫上这么多卖论文的，真有人买论文么？感觉没必要啊
已经有13人回复
-
哪位老哥知道今年的国自然具体哪一天放榜？
已经有7人回复
-
关于Filecode分析方法
已经有13人回复
-
各位道友，我要去昆明玩几天，回来见。
已经有8人回复
-
咱们一起用铁证分析2026国家社科基金中标与否
已经有22人回复
