ARNMD 88th Annual Conference

描述（申请人提供）：我们正处于基因组科学的革命之中，这场革命是如此深刻和前所未有，它将永远改变我们看待生物学和医学的方式，特别是在复杂的认知和行为功能的进化、大脑发育和基因-环境相互作用的机制、神经精神疾病的病因学、利用内源性神经干细胞来促进响应于损伤或疾病的动态组织重塑，以及开发新一代更具选择性和有效的药物表观基因组治疗试剂。表观遗传学是指一个以前未知的复杂分子机制的世界，这些机制需要协调基因表达谱的动态和连续变化，并部署功能性基因网络，以促进突触和神经网络可塑性，神经元稳态和适应性应激反应以及复杂行为特征的多代遗传，对多种神经系统疾病状态的易感性和对一系列多因素环境损伤的持久反应。发言者将讨论所有这些重要问题。会议的前半部分将集中在表观遗传学和大脑行为的关系。这将包括对基因网络，细胞过程和神经生物学系统的表观遗传调节的四个基本机制的概述，重点是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中的作用。接下来将探讨各种环境和内感受性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。接下来将研究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对表观基因组编程的影响，以用于以后的神经系统功能和适应。最后，关键的发展时期的作用，为塑造不断发展的表观基因组的组成部分，将提出其重要性，以确定神经系统的脆弱性，迟发性疾病将概述。会议的后半部分将集中在表观遗传学和神经精神疾病。的Xlinked形式的基因组印记的分子机制的表观遗传四分体的各种组件的作用将被突出和审查，特别强调这种等位基因特异性表观遗传的“标记”机制的作用，以及成人的大脑和行为功能。组蛋白密码子和核小体的组分的失调和高级染色质重塑对于重性抑郁症的病因学的重要性将被探讨。此后，多方面的线索，自闭症谱系障碍代表了一个基本的障碍，表观遗传机制和相关的神经回路介导的细胞身份，神经网络连接和社会行为的失调与父母之间的冲突，等位基因特异性表达和相关的区域脑功能的贡献将被检查。此外，支持DNA甲基化，甲基CpG结合蛋白和多方面的染色质代码在精神分裂症的病因组成部分的改变的作用将被概述。最后，复杂的表观遗传介导的改变在RNA调控电路和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异常扩增相关的RNA中间体将讨论与复杂和不断发展的疾病表型和新的个体疾病遗传模式相关的RNA显性疾病的新兴概念。所有演讲者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基因组设计治疗剂的重要性。

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.