Consequences of a peroxiredoxin 4 (Prdx4) deficiency on learning and memory in mice
Consequences of a peroxiredoxin 4 (Prdx4) deficiency on learning and memory in mice
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过氧化还原蛋白 4 (Prdx4) 缺乏对小鼠学习和记忆的影响
DOI：
10.1016/j.bbrc.2022.06.096
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发表时间：
2022
影响因子：
3.1
通讯作者：
Fujii Junichi
中科院分区：
文献类型：
--
作者：
Homma Takujiro;Fujiwara Hiroki;Osaki Tsukasa;Fujii Satoshi;Fujii Junichi
过氧化还原蛋白 4 (Prdx4) 负责内质网 (ER) 中合成的新蛋白质的氧化折叠。最近有人提出，内质网应激增加与神经退行性疾病有关，包括阿尔茨海默病。 Prdx4广泛分布于整个大脑，也在海马神经元和少突胶质细胞中表达，表明它与学习和记忆有关。我们之前建立了 Prdx4 敲除（KO）小鼠，但没有检查行为表型。在本研究中，我们基于 Morris 水迷宫和 Y 迷宫测试报告了 Prdx4-KO 小鼠的学习和记忆能力。研究结果表明，Prdx4-KO 小鼠在两项测试中均表现出较低的空间记忆能力。相反，旷场测试的结果表明 Prdx4-KO 小鼠的运动活性显着增加。然后，我们对 Prdx4-KO 小鼠的大脑进行 mRNA 分析，发现与 ER 相关降解 (ERAD) 机制相关的基因表达增加，这是维持 ER 稳态的重要蛋白质质量控制系统。最后，Prdx4-KO 小鼠大脑的蛋白质组学分析显示蛋白质表达异常，这被认为与神经元中的钙稳态和突触发生有关。我们的集体结果表明，Prdx4 消融扰乱了 ER 中的氧化蛋白折叠，从而导致神经元细胞中的 ER 稳态异常，最终导致空间记忆形成受损。
Peroxiredoxin 4 (Prdx4) is responsible for the oxidative folding of new proteins that are synthesized in the endoplasmic reticulum (ER). It has recently been suggested that increased ER stress is associated with neurodegenerative diseases, including Alzheimer's disease. Prdx4 is widely distributed throughout the brain, and is also expressed in hippocampal neurons and oligodendrocytes, suggesting that it is associated with learning and memory. We previously established Prdx4-knockout (KO) mice but did not examine the behavioral phenotypes. In the present study, we report on the learning and memory abilities of Prdx4-KO mice based on Morris water maze and the Y-maze tests. The findings indicate that Prdx4-KO mice showed a lower spatial memory ability in both tests. In contrast, the results of the open field test indicated that locomotor activity is significantly increased in Prdx4-KO mice. We then performed mRNA analyses of the brains of Prdx4-KO mice and found an increased expression of genes related to the ER-associated degradation (ERAD) mechanism, which is an important protein quality control system for the maintenance of ER homeostasis. Finally, proteomic analyses of the brains of Prdx4-KO mice showed an aberrant expression in the proteins, which have been suggested to be related to calcium homeostasis and synaptogenesis in neurons. Our collective results suggest that the Prdx4 ablation perturbs oxidative protein folding in the ER, thus leading to aberrant ER homeostasis in neuronal cells, ultimately leading to impaired spatial memory formation.