BACKGROUND 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. RESULTS 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. CONCLUSIONS 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.

中文翻译：

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STIM2保护海马蘑菇棘免受淀粉样蛋白的突触毒性。

背景技术阿尔茨海默氏病（AD）是失去记忆的疾病。蘑菇突触后突棘在记忆存储中起关键作用，蘑菇突突的丧失被认为与AD的记忆丧失有关。淀粉样蛋白生成肽的产生和淀粉样蛋白斑的积累是AD的病理标志之一。评估淀粉样蛋白对蘑菇刺稳定性的影响很重要。结果在这项研究中，我们使用淀粉样蛋白突触毒性的体外和体内模型来研究淀粉样蛋白肽对海马蘑菇棘的影响。我们发现，将Aβ42低聚物应用于海马培养物或将Aβ42低聚物直接注射到海马区会导致蘑菇棘减少和突触钙钙调蛋白依赖性激酶II（CaMKII）的活性。我们进一步发现，STIM2蛋白的表达可挽救CaMKII活性，并在体外和体内保护蘑菇刺免受淀粉样蛋白的毒性。结论获得的结果表明，在淀粉样蛋白突触毒性AD模型中，下调蘑菇棘突依赖STIM2的稳定性和降低突触CaMKII的活性是海马突触丧失的机制，该途径的调节剂/激活剂可能具有潜在的治疗价值。的。