ARNMD 88th Annual Conference

描述(申请人提供)：我们正处于一场如此深刻和前所未有的基因组科学革命中，它将永远改变我们看待生物学和医学的方式，特别是在以下方面：复杂认知和行为功能的演变、大脑发育和基因-环境相互作用的调控机制、神经精神疾病的病因学、利用内源性神经干细胞促进动态组织重塑以应对损伤或疾病，以及开发更具选择性和有效性的新一代药物表观治疗试剂。表观遗传学是指一个以前未知的复杂分子机制的世界，需要协调基因表达谱的动态和连续变化，以及部署功能基因网络以促进突触和神经网络的可塑性、神经元的动态平衡和适应性应激反应，以及复杂行为特征的多代遗传、对不同神经疾病状态的易感性和对一系列多因素环境侮辱的持久反应。演讲者将讨论所有这些开创性的问题。会议的前半部分将集中讨论表观遗传学和大脑行为关系。这将包括对基因网络、细胞过程和神经生物系统的表观遗传调控的四个基本机制的概述，重点放在这些机制在促进人类大脑形式和功能在健康和特定疾病状态下的爆炸性创新方面的作用。接下来将探讨各种环境和感觉应激反应以及对这些条件的独特和可塑性表观遗传适应性反应的作用。接下来将检查产前和围产期护理的影响以及神经内分泌功能的个体差异，以便为以后的神经系统功能和适应对表观基因组进行编程。最后，将介绍关键发育期在塑造进化中的表观基因组组件方面的作用，并概述其对确定神经系统对迟发性疾病的脆弱性的重要性。会议的后半部分将集中讨论表观遗传学和神经精神疾病。表观遗传四分体在X连锁形式的基因组印记中的分子机制的不同组成部分的作用将被强调和回顾，特别强调这种等位基因特定的表观遗传“标记”机制对发育以及成人大脑和行为功能的作用。接下来将探讨组蛋白编码和核小体成分的去调控以及高阶染色质重塑对主要抑郁障碍的病因学的重要性。此后，将研究自闭症谱系障碍代表表观遗传机制的根本性障碍的多方面线索，以及与调节细胞识别、神经网络连通性和社会行为的神经回路相关的放松调控，这些神经回路与基因内冲突有关，在父母对等位基因表达的贡献与相关的区域大脑功能之间存在冲突。此外，还将概述DNA甲基化改变、甲基CpG结合蛋白和染色质密码多方面成分在精神分裂症病因中的作用的支持。最后，将讨论复杂的表观遗传介导的改变在RNA调节电路和DNA的三级结构中的作用：与神经退行性疾病的三核苷酸重复子集中存在的微卫星重复序列的异常扩张相关的RNA中间产物的作用，以及与复杂和进化的疾病表型和新的个体疾病遗传模式相关的RNA显性疾病的新概念。所有发言者都将强调这些新颖和最先进的概念对于开发独特类别的药物表观组学设计者治疗剂的重要性。

DESCRIPTION (provided by applicant): We are in the midst of a revolution in the genomic sciences so profound and unprecedented that it will forever change the way we view biology and medicine, particularly with respect to the evolution of complex cognitive and behavioral functions, the mechanisms governing brain development and gene-environmental interactions, the etiology of neuropsychiatric diseases, the harnessing of endogenous neural stem cells to promote dynamic tissue remodeling in response to injury or disease and the development of new generations of more selective and efficacious pharmacoepigenomic therapeutic reagents. Epigenetics refers to a previously uncharted world of sophisticated molecular mechanisms required to orchestrate dynamic and continuous changes in the profiles of gene expression and the deployment of functional gene networks to promote synaptic and neural network plasticity, neuronal homeostasis and adaptive stress responses as well as multigenerational inheritance of complex behavioral traits, susceptibility to diverse neurological disease states and enduring responses to a spectrum of multifactorial environmental insults. The speakers will address all of these seminal issues. The first half of the meeting will focus on epigenetics and brain-behavior relationships. This will include an overview of the four cardinal mechanisms of epigenetic regulation of gene networks, cellular processes and neurobiological systems with an emphasis on the role of these mechanisms for promoting explosive innovations in human brain form and function in health and specific disease states. The role of various environmental and interoceptive stress responses and unique and plastic epigenetic adaptive responses to these conditions will next be explored. The influence of prenatal and perinatal care and individual differences in neuroendocrine functions for programming the epigenome for later nervous system functioning and adaptations will next be examined. Finally, the role of critical developmental periods for sculpting components of the evolving epigenome will be presented and its importance for determining the vulnerability of the nervous system to late-onset diseases will be outlined. The second half of the meeting will focus on epigenetics and neuropsychiatric diseases. The role of various components of the epigenetic tetrad of molecular mechanisms involved in an Xlinked form of genomic imprinting will be highlighted and reviewed with particular emphasis on the role of this allele-specific epigenetic "tagging" mechanism for developmental as well as adult brain and behavioral functions. The importance of deregulation of components of the histone code and nucleosome and higher-order chromatin remodeling for the etiology of major depressive disorders will next be explored. Thereafter, the multifaceted clues that autism spectrum disorders represents a fundamental disorder of epigenetic mechanisms and associated deregulation of neural circuits mediating cell identity, neural network connectivity and social behaviors related to intragenomic conflicts between parental contributions to allelespecific expression and associated regional brain functions will be examined. Further, support for the role of alterations in DNA methylation, methyl CpG binding proteins and multifaceted components of the chromatin code in the etiology of schizophrenia will be outlined. Finally, the role of complex epigenetically-mediated alterations in RNA regulatory circuitry and in the tertiary structure of DNA: RNA intermediates associated with abnormal expansion of microsatellite repeats present in the trinucleotide repeat subset of neurodegenerative disorders will be discussed with regard to the emerging concept of RNA-dominant diseases associated with intricate and evolving disease phenotypes and novel modes of individual disease inheritance. All speakers will emphasize the importance of these novel and state-of-the-art concepts for the development of unique classes of pharmacoepigenomic designer therapeutic agents.