Department of Psychiatry, Columbia University, New York, NY, United States; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, United States.
Neurosci Biobehav Rev. 2017 Dec;83:63-71. doi: 10.1016/j.neubiorev.2017.10.004. Epub 2017 Oct 7.
Coordinated changes in gene expression are critical for synaptic plasticity supporting learning, memory, and optimal cognitive task performance. These gene expression changes are not only mediated by signaling pathways that activate transcription factors, but also by chromatin modifications that influence the accessibility of the transcriptional machinery to specific genomic regions. During the past decade, evidence accumulated that alterations in chromatin-based epigenetic regulation of gene expression are linked to cognitive dysfunctions in the ageing or neurodegenerating brain as well as to cognitive dysfunctions resulting from chronic stress exposure. This review summarizes the results of studies that unraveled a role of histone modifying enzymes and histone modifications in normal and impaired learning and memory, and in the disruption of executive cognitive task performance. It emphasizes the different roles of specific class I histone deacetylases (HDACs) in cognitive processes governed by the hippocampus and prefrontal cortex and discusses the potential therapeutic implications of targeting them to hold the progression of disease-related cognitive dysfunctions.
协调基因表达的变化对于支持学习、记忆和最佳认知任务表现的突触可塑性至关重要。这些基因表达变化不仅由激活转录因子的信号通路介导，还由影响转录机制对特定基因组区域可及性的染色质修饰介导。在过去的十年中，有证据表明，染色质基表观遗传调控基因表达的改变与衰老或神经退行性大脑中的认知功能障碍以及慢性应激暴露导致的认知功能障碍有关。
本综述总结了阐明组蛋白修饰酶和组蛋白修饰在正常和受损的学习和记忆以及执行认知任务表现中断中的作用的研究结果。它强调了特定 I 类组蛋白去乙酰化酶 (HDACs) 在海马体和前额叶皮层控制的认知过程中的不同作用，并讨论了针对它们以阻止与疾病相关的认知功能障碍进展的潜在治疗意义。
