Epigenetic mechanisms in experience-driven memory formation and behavior.
Epigenetic mechanisms in experience-driven memory formation and behavior.
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DOI：
10.2217/epi.11.86
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发表时间：
2011-10
期刊：
影响因子：
3.8
通讯作者：
Lubin FD
中科院分区：
文献类型：
--
作者：
Puckett RE;Lubin FD
表观遗传机制长期以来一直与伴随正常神经元发育和细胞分化的基因表达变化的调节有关;然而，直到最近，这些机制才被认为在成人大脑中是静态安静的。行为神经科学家现在已经开始研究这些表观遗传机制，作为CNS中基因转录变化的潜在调节因子，从而促进突触可塑性和长期记忆（LTM）的形成。来自学习和记忆动物模型的实验证据表明，活性染色质重塑发生在终末分化的有丝分裂后神经元中，表明这些分子过程确实密切参与LTM形成的几个阶段，包括巩固，再巩固和消退。这种染色质修饰包括组蛋白的磷酸化、乙酰化和甲基化以及相关DNA的甲基化，以随后影响由学习触发的转录基因读出。本文探讨了这种学习引起的表观遗传变化如何有助于LTM的形成和影响行为。特别是，这篇文章是一个调查的特定表观遗传机制，已被证明可以调节基因表达的转录因子和生长因子在中枢神经系统中，这是关键的LTM的形成和存储，以及异常的表观遗传加工可以有助于心理状态，如精神分裂症和药物成瘾。总之，本文中强调的研究结果支持表观遗传机制在成人CNS中的新作用，其作为LTM形成和成人行为所需的基因转录变化的潜在关键分子调节因子。
Epigenetic mechanisms have long been associated with the regulation of gene-expression changes accompanying normal neuronal development and cellular differentiation; however, until recently these mechanisms were believed to be statically quiet in the adult brain. Behavioral neuroscientists have now begun to investigate these epigenetic mechanisms as potential regulators of gene-transcription changes in the CNS subserving synaptic plasticity and long-term memory (LTM) formation. Experimental evidence from learning and memory animal models has demonstrated that active chromatin remodeling occurs in terminally differentiated postmitotic neurons, suggesting that these molecular processes are indeed intimately involved in several stages of LTM formation, including consolidation, reconsolidation and extinction. Such chromatin modifications include the phosphorylation, acetylation and methylation of histone proteins and the methylation of associated DNA to subsequently affect transcriptional gene readout triggered by learning. The present article examines how such learning-induced epigenetic changes contribute to LTM formation and influence behavior. In particular, this article is a survey of the specific epigenetic mechanisms that have been demonstrated to regulate gene expression for both transcription factors and growth factors in the CNS, which are critical for LTM formation and storage, as well as how aberrant epigenetic processing can contribute to psychological states such as schizophrenia and drug addiction. Together, the findings highlighted in this article support a novel role for epigenetic mechanisms in the adult CNS serving as potential key molecular regulators of gene-transcription changes necessary for LTM formation and adult behavior.