训练后抑制 I 类组蛋白去乙酰化酶可增强海马内长期物体位置记忆。
Post-training intrahippocampal inhibition of class I histone deacetylases enhances long-term object-location memory.
机构信息
Neuroscience Graduate Group, Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
出版信息
Learn Mem. 2011 May 16;18(6):367-70. doi: 10.1101/lm.2097411. Print 2011 Jun.
Abstract
Long-term memory formation involves covalent modification of the histone proteins that package DNA. Reducing histone acetylation by mutating histone acetyltransferases impairs long-term memory, and enhancing histone acetylation by inhibiting histone deacetylases (HDACs) improves long-term memory. Previous studies using HDAC inhibitors to enhance long-term memory have focused on the fear-conditioning task using broad-spectrum HDAC inhibitors. We have found that post-training intrahippocampal administration of the broad-spectrum HDAC inhibitor trichostatin A (TSA) or the class I HDAC-selective inhibitor MS275 enhances long-term object-location memory, supporting a role for class I HDACs in the enhancement of hippocampus-dependent memory induced by HDAC inhibition.
摘要
长期记忆的形成涉及到组蛋白的共价修饰，这些组蛋白将 DNA 包装起来。通过突变组蛋白乙酰转移酶降低组蛋白乙酰化会损害长期记忆，而通过抑制组蛋白去乙酰化酶 (HDACs) 增强组蛋白乙酰化可以改善长期记忆。先前使用 HDAC 抑制剂增强长期记忆的研究主要集中在使用广谱 HDAC 抑制剂的恐惧条件反射任务上。我们发现，在训练后海马内给予广谱 HDAC 抑制剂 Trichostatin A (TSA) 或 I 类 HDAC 选择性抑制剂 MS275 可增强长期物体位置记忆，这表明 I 类 HDACs 在 HDAC 抑制诱导的海马依赖性记忆增强中起作用。
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