Smrt Richard D, Zhao Xinyu
Department of Neuroscience, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, USA.
Front Biol (Beijing). 2010 Aug;5(4):304-323. doi: 10.1007/s11515-010-0650-0.
Dendrites and the dendritic spines of neurons play key roles in the connectivity of the brain and have been recognized as the locus of long-term synaptic plasticity, which is correlated with learning and memory. The development of dendrites and spines in the mammalian central nervous system is a complex process that requires specific molecular events over a period of time. It has been shown that specific molecules are needed not only at the spine's point of contact, but also at a distance, providing signals that initiate a cascade of events leading to synapse formation. The specific molecules that act to signal neuronal differentiation, dendritic morphology, and synaptogenesis are tightly regulated by genetic and epigenetic programs. It has been shown that the dendritic spine structure and distribution are altered in many diseases, including many forms of mental retardation (MR), and can also be potentiated by neuronal activities and an enriched environment. Because dendritic spine pathologies are found in many types of MR, it has been proposed that an inability to form normal spines leads to the cognitive and motor deficits that are characteristic of MR. Epigenetic mechanisms, including DNA methylation, chromatin remodeling, and the noncoding RNA-mediated process, have profound regulatory roles in mammalian gene expression. The study of epigenetics focuses on cellular effects that result in a heritable pattern of gene expression without changes to genomic encoding. Despite extensive efforts to understand the molecular regulation of dendrite and spine development, epigenetic mechanisms have only recently been considered. In this review, we will focus on epigenetic mechanisms that regulate the development and maturation of dendrites and spines. We will discuss how epigenetic alterations could result in spine abnormalities that lead to MR, such as is seen in fragile X and Rett syndromes. We will also discuss both general methodology and recent technological advances in the study of neuronal dendrites and spines.
神经元的树突和树突棘在大脑的连接中起着关键作用，并且已被公认为是长期突触可塑性的位点，这与学习和记忆相关。哺乳动物中枢神经系统中树突和树突棘的发育是一个复杂的过程，需要在一段时间内发生特定的分子事件。已经表明，不仅在树突棘的接触点，而且在一定距离处都需要特定的分子，这些分子提供启动一系列导致突触形成的事件的信号。作用于神经元分化、树突形态和突触形成信号的特定分子受到遗传和表观遗传程序的严格调控。已经表明，在包括多种形式的智力迟钝（MR）在内的许多疾病中，树突棘的结构和分布会发生改变，并且也可以通过神经元活动和丰富的环境得到增强。由于在多种类型的MR中都发现了树突棘病变，因此有人提出，无法形成正常的树突棘会导致MR特有的认知和运动缺陷。表观遗传机制，包括DNA甲基化、染色质重塑和非编码RNA介导的过程，在哺乳动物基因表达中具有深远的调控作用。表观遗传学研究集中在导致基因表达可遗传模式而基因组编码不变的细胞效应上。尽管人们为了解树突和树突棘发育的分子调控付出了巨大努力，但表观遗传机制直到最近才被考虑。在这篇综述中，我们将重点关注调控树突和树突棘发育和成熟的表观遗传机制。我们将讨论表观遗传改变如何导致导致MR的树突棘异常，如在脆性X综合征和雷特综合征中所见。我们还将讨论神经元树突和树突棘研究中的一般方法和最新技术进展。
