Multiple studies have found that increasing histone acetylation by means of histone deacetylase inhibitor (HDACi) treatment can ameliorate memory and rescue cognitive impairments, but their mode of action is not fully understood. In particular, it is unclear how HDACis, applied systemically and devoid of genomic target selectivity, would specifically improve memory-related molecular processes. One theory for such specificity is called cognitive epigenetic priming (CEP), according to which HDACis promote memory by facilitating the expression of neuroplasticity-related genes that have been stimulated by learning itself. In this review, we summarize the experimental evidence in support of CEP, describe newly discovered off-target effects of HDACis and highlight similarities between drug-induced and naturally occurring CEP. Understanding the underlying mechanisms of CEP is important in light of the preclinical premise of HDACis as cognitive enhancers.

多项研究发现，通过组蛋白脱乙酰基酶抑制剂（HDACi）处理增加组蛋白乙酰化可以改善记忆力并挽救认知障碍，但其作用方式尚不完全清楚。尤其是，目前尚不清楚全身应用HDAC且没有基因组靶点选择性的HDAC如何特别改善与记忆有关的分子过程。一种针对这种特异性的理论称为认知表观遗传启动（CEP），根据该理论，HDACis通过促进已被自身学习刺激的神经可塑性相关基因的表达来促进记忆。在这篇综述中，我们总结了支持CEP的实验证据，描述了新发现的HDACis脱靶效应，并强调了药物诱导的CEP与自然发生的CEP之间的相似性。