Liu Liang, van Groen Thomas, Kadish Inga, Tollefsbol Trygve O
Department of Biology, University of Alabama at Birmingham, 175 Campbell Hall, 1300 University Boulevard, Birmingham, AL 35294-1170, USA.
Neurobiol Aging. 2009 Apr;30(4):549-60. doi: 10.1016/j.neurobiolaging.2007.07.020. Epub 2007 Sep 11.
Learning and memory are two of the fundamental cognitive functions that confer us the ability to accumulate knowledge from our experiences. Although we use these two mental skills continuously, understanding the molecular basis of learning and memory is very challenging. Methylation modification of DNA is an epigenetic mechanism that plays important roles in regulating gene expression, which is one of the key processes underlying the functions of cells including neurons. Interestingly, a genome-wide decline in DNA methylation occurs in the brain during normal aging, which coincides with a functional decline in learning and memory with age. It has been speculated that DNA methylation in neurons might be involved in memory coding. However, direct evidence supporting the role of DNA methylation in memory formation is still under investigation. This particular function of DNA methylation has not drawn wide attention despite several important studies that have provided supportive evidence for the epigenetic control of memory formation. To facilitate further exploration of the epigenetic basis of memory function, we will review existing studies on DNA methylation that are related to the development and function of the nervous system. We will focus on studies illustrating how DNA methylation regulates neural activities and memory formation via the control of gene expression in neurons, and relate these studies to various age-related neurological disorders that affect cognitive functions.
学习和记忆是赋予我们从经历中积累知识能力的两项基本认知功能。尽管我们持续运用这两种心智技能，但理解学习和记忆的分子基础极具挑战性。DNA甲基化修饰是一种表观遗传机制，在调节基因表达中发挥重要作用，而基因表达是包括神经元在内的细胞功能的关键过程之一。有趣的是，在正常衰老过程中，大脑中会出现全基因组范围内的DNA甲基化下降，这与随着年龄增长学习和记忆功能的衰退相吻合。据推测，神经元中的DNA甲基化可能参与记忆编码。然而，支持DNA甲基化在记忆形成中作用的直接证据仍在研究中。尽管有几项重要研究为记忆形成的表观遗传控制提供了支持性证据，但DNA甲基化的这一特殊功能尚未引起广泛关注。为便于进一步探索记忆功能的表观遗传基础，我们将回顾现有的与神经系统发育和功能相关的DNA甲基化研究。我们将重点关注说明DNA甲基化如何通过控制神经元中的基因表达来调节神经活动和记忆形成的研究，并将这些研究与影响认知功能的各种与年龄相关的神经疾病联系起来。
