STIM2 protects hippocampal mushroom spines from amyloid synaptotoxicity.
STIM2 protects hippocampal mushroom spines from amyloid synaptotoxicity.
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DOI：
10.1186/s13024-015-0034-7
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发表时间：
2015-08-15
影响因子：
15.1
通讯作者：
Bezprozvanny I
中科院分区：
文献类型：
--
作者：
Popugaeva E;Pchitskaya E;Speshilova A;Alexandrov S;Zhang H;Vlasova O;Bezprozvanny I
阿尔茨海默病（AD）是一种记忆丧失的疾病。蘑菇突触后棘在记忆储存中起着关键作用，并且已经提出蘑菇棘的丢失与AD中的记忆丧失有关。淀粉样肽的产生和淀粉样斑块的积累是AD的病理特征之一。研究淀粉样蛋白对蘑菇刺稳定性的影响具有重要意义。在这项研究中，我们使用在体外和体内模型的淀粉样突触毒性，以调查的影响，淀粉样肽对海马蘑菇棘。我们发现，将Aβ42寡聚体应用于海马培养物或将Aβ42寡聚体直接注射到海马区域导致蘑菇刺减少和突触钙-钙调蛋白依赖性激酶II（CaMK II）活性降低。我们进一步发现，STIM 2蛋白的表达拯救了CaMKII活性，并在体外和体内保护蘑菇刺免受淀粉样蛋白毒性。研究结果提示，STIM 2依赖的蘑菇刺稳定性下调和突触CaMK Ⅱ活性降低是淀粉样蛋白突触毒性AD模型中海马突触丢失的机制之一，该通路的调节剂/激活剂可能对AD的治疗具有潜在的治疗价值。本文的在线版本（doi：10.1186/s13024-015-0034-7）包含补充材料，可供授权用户使用。
Alzheimer disease (AD) is a disease of lost memories. Mushroom postsynaptic spines play a key role in memory storage, and loss of mushroom spines has been proposed to be linked to memory loss in AD. Generation of amyloidogenic peptides and accumulation of amyloid plaques is one of the pathological hallmarks of AD. It is important to evaluate effects of amyloid on stability of mushroom spines. In this study we used in vitro and in vivo models of amyloid synaptotoxicity to investigate effects of amyloid peptides on hippocampal mushroom spines. We discovered that application of Aβ42 oligomers to hippocampal cultures or injection of Aβ42 oligomers directly into hippocampal region resulted in reduction of mushroom spines and activity of synaptic calcium-calmodulin-dependent kinase II (CaMKII). We further discovered that expression of STIM2 protein rescued CaMKII activity and protected mushroom spines from amyloid toxicity in vitro and in vivo. Obtained results suggest that downregulation of STIM2-dependent stability of mushroom spines and reduction in activity of synaptic CaMKII is a mechanism of hippocampal synaptic loss in AD model of amyloid synaptotoxicity and that modulators/activators of this pathway may have a potential therapeutic value for treatment of AD. The online version of this article (doi:10.1186/s13024-015-0034-7) contains supplementary material, which is available to authorized users.