α2-Antiplasmin (α2AP), a principal physiological plasmin inhibitor, is mainly produced by the liver and kidneys, but it is also expressed in several parts of the brain, including the hippocampus and cerebral cortex. Our previous study demonstrated that α2AP knockout mice exhibit spatial memory impairment in comparison to wild-type mice, suggesting that α2AP is necessary for the fetal and/or neonatal development of the neural network for spatial memory. However, it is still unclear whether α2AP plays a role in the memory process. The present study demonstrated that adult hippocampal neurogenesis and remote spatial memory were enhanced by the injection of an anti-α2AP neutralizing antibody in WT mice, while the injection of α2AP reduced hippocampal neurogenesis and impaired remote spatial memory, suggesting that α2AP is a negative regulator in memory processing. The present study also found that the levels of α2AP in the brains of old mice were higher than those in young mice, and a negative correlation between the α2AP level and spatial working memory. In addition, aging-dependent brain oxidative stress and hippocampal inflammation were attenuated by α2AP deficiency. Thus, an age-related increase in α2AP might cause cognitive decline accompanied by brain oxidative stress and neuroinflammation. Taken together, our findings suggest that α2AP is a key regulator of the spatial memory process, and that it may represent a promising target to effectively regulate healthy brain aging.

中文翻译：

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α2-抗纤溶蛋白作为空间记忆过程和年龄相关性认知衰退的潜在调节剂

α2-抗纤溶酶（α2AP）是一种主要的生理纤溶酶抑制剂，主要由肝脏和肾脏产生，但也表达于大脑的多个部位，包括海马和大脑皮层。我们以前的研究表明，与野生型小鼠相比，α2AP基因敲除小鼠表现出空间记忆障碍，这表明α2AP对胎儿和/或新生儿神经网络的空间记忆至关重要。但是，尚不清楚α2AP是否在记忆过程中起作用。本研究表明，通过在WT小鼠中注射抗α2AP中和抗体可以增强成年海马神经发生和远程空间记忆，而注射α2AP可以减少海马神经发生并损害远程空间记忆，这表明α2AP在记忆处理中是负调节剂。本研究还发现，老年小鼠大脑中的α2AP水平高于年轻小鼠，并且α2AP水平与空间工作记忆呈负相关。此外，α2AP缺乏可减轻衰老相关的脑氧化应激和海马炎症。因此，与年龄相关的α2AP升高可能导致认知能力下降，并伴有脑氧化应激和神经炎症。综上所述，我们的发现表明，α2AP是空间记忆过程的关键调节剂，它可能代表有效调节健康大脑衰老的有希望的目标。α2AP水平与空间工作记忆之间呈负相关。此外，α2AP缺乏可减轻衰老相关的脑氧化应激和海马炎症。因此，与年龄相关的α2AP升高可能导致认知能力下降，并伴有脑部氧化应激和神经炎症。综上所述，我们的发现表明，α2AP是空间记忆过程的关键调节剂，它可能代表有效调节健康大脑衰老的有希望的目标。α2AP水平与空间工作记忆之间呈负相关。此外，α2AP缺乏可减轻衰老相关的脑氧化应激和海马炎症。因此，与年龄相关的α2AP升高可能导致认知能力下降，并伴有脑氧化应激和神经炎症。综上所述，我们的发现表明，α2AP是空间记忆过程的关键调节剂，它可能代表有效调节健康大脑衰老的有希望的目标。