We previously showed that death-associated protein kinase 1 (DAPK1) expression is increased in hippocampal tissue in a mouse model of major depressive disorde and is related to cognitive dysfunction in Alzheimer's disease. In addition, depression is a risk factor for developing Alzheimer's disease, as well as an early clinical manifestation of Alzheimer's disease. Meanwhile, cognitive dysfunction is a distinctive feature of major depressive disorder. Therefore, DAPK1 may be related to cognitive dysfunction in major depressive disorder. In this study, we established a mouse model of major depressive disorder by housing mice individually and exposing them to chronic, mild, unpredictable stressors. We found that DAPK1 and tau protein levels were increased in the hippocampal CA3 area, and tau was hyperphosphorylated at Thr231, Ser262, and Ser396 in these mice. Furthermore, DAPK1 shifted from axonal expression to overexpression on the cell membrane. Exercise and treatment with the antidepressant drug citalopram decreased DAPK1 expression and tau protein phosphorylation in hippocampal tissue and improved both depressive symptoms and cognitive dysfunction. These results indicate that DAPK1 may be a potential reason and therapeutic target of cognitive dysfunction in major depressive disorder.

中文翻译：

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死亡相关蛋白激酶 1 与重度抑郁症的认知功能障碍有关。

我们之前表明，在重度抑郁症小鼠模型中，死亡相关蛋白激酶 1 (DAPK1) 表达在海马组织中增加，并且与阿尔茨海默病的认知功能障碍有关。此外，抑郁症是患阿尔茨海默病的危险因素，也是阿尔茨海默病的早期临床表现。同时，认知功能障碍是重度抑郁症的一个显着特征。因此，DAPK1可能与重度抑郁症的认知功能障碍有关。在这项研究中，我们通过单独饲养小鼠并将它们暴露于慢性、轻度、不可预测的压力源中，建立了重度抑郁症小鼠模型。我们发现海马 CA3 区 DAPK1 和 tau 蛋白水平升高，tau 在 Thr231、Ser262、和这些小鼠中的 Ser396。此外，DAPK1 从轴突表达转变为细胞膜上的过度表达。运动和抗抑郁药西酞普兰治疗降低了海马组织中的 DAPK1 表达和 tau 蛋白磷酸化，改善了抑郁症状和认知功能障碍。这些结果表明 DAPK1 可能是重度抑郁症认知功能障碍的潜在原因和治疗靶点。