ARNMD 88th Annual Conference

ARNMD第88届年会

• 批准号: 7613904
• 负责人: Jack David Barchas
• 金额: $ 3.5万
• 依托单位: ASSOCIATION FOR RESEARCH/NERV & MENT DIS
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-05 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7613904
• 关键词: Address; Adult; Alleles; Arts; Behavioral; Binding Proteins; Biological; Biological Markers; Biological Neural Networks; Biology; Brain; Cell physiology; Cells; Chromatin; Clinical; Code; Cognitive; Complex; Conflict (Psychology); DNA Methylation; DNA Structure; Development; Disease; Early Diagnosis; Epigenetic Process; Etiology; Evolution; Fostering; Future; Gene Expression; Gene Expression Regulation; Generations; Genes; Genomic Imprinting; Genomics; Goals; Health; Histone Code; Homeostasis; Human; Individual; Individual Differences; Knowledge; Learning; Major Depressive Disorder; Measures; Mediating; Medicine; Memory; Microsatellite Repeats; Molecular; Nerve Degeneration; Nervous System Physiology; Nervous system structure; Neurobiology; Neurodegenerative Disorders; Neurologist; Neuronal Plasticity; Neurosciences; Neurosecretory Systems; Nucleosomes; Pathogenesis; Perinatal Care; Plastics; Predisposition; Psyche structure; Psychiatrist; Publications; RNA; Reagent; Research; Risk Assessment; Role; Schizophrenia; Science; Seminal; Social Behavior; Synapses; System; Therapeutic; Therapeutic Agents; Tissues; Translational Research; Treatment Efficacy; Trinucleotide Repeats; autism spectrum disorder; base; bench to bedside; biological adaptation to stress; brain behavior; career; chromatin remodeling; clinical care; critical developmental period; critical period; disease phenotype; disorder risk; epigenomics; improved; innovation; interest; late disease onset; meetings; member; nerve stem cell; nervous system disorder; neural circuit; neurodevelopment; neuropsychiatry; novel; prenatal influence; programs; psychobiology; response; response to injury; stem cell biology; symposium; trait

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.

描述（由申请人提供）：我们正处于基因组科学的一场革命之中，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促进 响应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世界，需要协调基因表达谱的动态和连续变化以及功能基因网络的部署，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、对不同神经系统疾病状态的易感性和持久反应 一系列多因素环境损害。演讲者将讨论所有这些重大问题。会议的前半部分将重点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学系统的表观遗传调控的四种主要机制的概述，重点是这些机制在促进健康和特定疾病状态下人脑形式和功能的爆炸性创新中的作用。接下来将探讨各种环境和内感受应激反应的作用以及对这些条件的独特和可塑的表观遗传适应性反应。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的编程，以促进以后的神经系统功能和适应。最后，将介绍关键发育时期对于塑造不断演变的表观基因组成分的作用，并概述其对于确定神经系统对迟发性疾病的脆弱性的重要性。会议的下半场将重点讨论表观遗传学和神经精神疾病。将强调和回顾涉及X连锁形式的基因组印记的表观遗传四联体分子机制的各个组成部分的作用，特别强调这种等位基因特异性表观遗传“标签”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密码和核小体成分的失调以及高阶染色质重塑对于重度抑郁症病因学的重要性。此后，自闭症谱系障碍代表了表观遗传机制的基本障碍，以及介导细胞身份的神经回路的失调、神经网络连接和与父母对等位基因特异性表达的贡献和相关区域大脑功能之间的基因组内冲突相关的社会行为的多方面线索将得到检查。此外，还将概述 DNA 甲基化、甲基 CpG 结合蛋白和染色质密码多方面成分的改变在精神分裂症病因学中的作用。最后，将讨论RNA调节回路和DNA三级结构中复杂的表观遗传介导的改变的作用：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张相关的RNA中间体，将讨论与复杂和不断发展的疾病表型和新模式相关的RNA主导疾病的新兴概念。 个体疾病遗传。所有演讲者都将强调这些新颖且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。