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首页> 外文期刊>Genes, brain, and behavior >Impaired cognitive function and reduced anxiety-related behavior in a promyelocytic leukemia (PML) tumor suppressor protein-deficient mouse.
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Impaired cognitive function and reduced anxiety-related behavior in a promyelocytic leukemia (PML) tumor suppressor protein-deficient mouse.

机译：早幼粒细胞白血病（PML）肿瘤抑制蛋白缺陷型小鼠的认知功能受损和焦虑相关行为减少。

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The promyelocytic leukemia (PML) protein is a tumor suppressor factor mostly known by its involvement in acute promyelocytic leukemia (APL). Interestingly, recent studies have provided evidence that, in the central nervous system, PML is involved in neurogenesis. However, prospective studies of PML in brain are lacking. To further understand the role of PML in the mammalian brain, we studied plasticity and behavioral changes in PML knockout mice. If PML is involved in neurogenesis, and neurogenesis is an important process for proper brain development as well as learning and memory functions, we hypothesized that PML might have a role in plasticity and cognition. Behavioral studies demonstrated that PML knockout mice present abnormalities in conditioned learning and spatial memory, as determined by fear conditioning and Morris water maze tasks. Experiments to determine normal exploratory behavior interestingly revealed that PML knockout mice present reduced anxiety-related responses as compared to control animals. This was confirmed when PML knockout mice spent more time in the open arms of an elevated plus-maze, which is an indication of decreased anxiety. Additionally, impairments in hippocampus-dependent learning were mirrored by altered long-term plasticity at Schaffer collateral-CA1 synapses. We now provide the first evidence for an important role of PML in the brain, indicating that PML might have a role in synaptic plasticity and associated behavioral processes.
机译：早幼粒细胞白血病（PML）蛋白是一种肿瘤抑制因子，主要因其参与急性早幼粒细胞白血病（APL）而闻名。有趣的是，最近的研究提供了证据，表明在中枢神经系统中，PML与神经发生有关。然而，缺乏对PML在大脑中的前瞻性研究。为了进一步了解PML在哺乳动物大脑中的作用，我们研究了PML基因敲除小鼠的可塑性和行为变化。如果PML参与神经发生，而神经发生是正常大脑发育以及学习和记忆功能的重要过程，我们假设PML可能在可塑性和认知中起作用。行为研究表明，PML基因敲除小鼠表现出条件学习和空间记忆异常，这由恐惧条件和莫里斯水迷宫任务确定。确定正常探索行为的实验有趣地显示，与对照动物相比，PML基因敲除小鼠表现出减少的焦虑相关反应。当PML基因敲除小鼠在高架迷宫的张开臂​​上花费更多的时间时，这一点得到了证实，这表明焦虑降低了。此外，沙弗侧支CA1突触的长期可塑性改变反映了海马依赖性学习障碍。现在，我们提供了PML在大脑中重要作用的第一个证据，表明PML可能在突触可塑性和相关的行为过程中起作用。

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