Neuroregulators

神经调节剂

• 批准号: 6850627
• 负责人: PAUL M PLOTSKY
• 金额: $ 15.3万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6850627
• 关键词: Macaca mulatta; age difference; behavioral /social science research tag; corticotropin releasing factor; developmental neurobiology; developmental psychology; disease /disorder proneness /risk; early experience; environmental stressor; gender difference; hormone receptor; hypothalamic pituitary adrenal axis; laboratory rat; major depression; mother deprivation; neural plasticity; neuroanatomy; neuroendocrine system; neuroregulation; psychological stressor; stress

Project 0001 of the Emory University Silvio O. Conte Center for the Neuroscience of Mental Disorders (CCNMD) represents an integral component of the overall Center. We have proposed four studies that in concept or data generated are interrelated to one another and to other basic and clinical projects in this Center proposal. The primary focus is on early life stress induced alterations in neurocircuits and their function. Briefly, the first study (Investigator: Paul M. Plotsky, PhD) extends our knowledge of sensitive periods in development and the sequence of neurocircuits that change in response to an unstable early environment using variations on the rat neonatal maternal separation paradigm. The studies will use behavioral, neuroendocrine (HPA axis function) and CNS gene expression as endpoints. We seek to clarify the relationship between behavioral alterations, HPA axis changes, and adaptations of other central circuits. The second study (Investigators: Kerry Ressler, MD, PhD, & Paul M. Plotsky, PhD) will directly address the role of early life stress induced up-regulation of extra-hypothalamic CRF systems and the locus coeruleus NE system using targeted retrovirus-mediated gene transfer of the rat CRF or tyrosine hydroxylase (TH) genes during different neonatal periods or in adulthood. The third study (Investigators: Donald Rainnie, Ph.DI, & Paul M. Plotsky, PhD)will address important functional issues by assessing how early life stress may alter the balance of signaling in the bed nucleus of the stria terminalis (BNST) such that stress-induced 5-HT input to this region shows a reversal from a stimulatory to inhibitory pattern resulting in a potentially maladaptive response to subsequent stressors. The fourth study (Investigators: M. Mar Sanchez, PhD, & Paul M. Plotsky, PhD) will begin postmortem analyses of gene expression and receptor binding in a sampling of rhesus monkey brains from our existing cohorts (see Conte Monkey Core 9003). Together, these components provide a multifaceted investigation of the long-term consequences of early life stress on neurocircuits in the rat and rhesus models. These data will be important for comparison and interpretation of imaging data obtained in the human studies. Furthermore, they may hold important theoretical implications and clinical relevance. The convergence of excellent animal models, sophisticated scientific questions, cutting edge techniques, and extraordinary expertise among the participants of this project and the Conte Center permit us to address the question of how early life stress affects selected neurocircuits and subsequent behavioral and neuroendocrine in a systematic way.

埃默里大学Silvio O. Conte神经科学中心（CCNMD）的项目0001代表了整个中心的组成部分。我们提出了四项研究，其中生成的概念或数据与该中心提案中的其他基本和临床项目相互关联。主要的重点是早期生活压力引起的神经环节及其功能的改变。简而言之，第一项研究（研究者：Paul M. Plotsky，PhD）扩展了我们对发育敏感时期的了解以及使用大鼠新生儿母亲分离范式的变化，这些变化会改变对不稳定的早期环境的变化。研究将使用行为，神经内分泌 （HPA轴函数）和CNS基因表达作为终点。我们试图阐明行为改变，HPA轴变化和其他中央电路的适应之间的关系。 The second study (Investigators: Kerry Ressler, MD, PhD, & Paul M. Plotsky, PhD) will directly address the role of early life stress induced up-regulation of extra-hypothalamic CRF systems and the locus coeruleus NE system using targeted retrovirus-mediated gene transfer of the rat CRF or tyrosine hydroxylase (TH) genes during different neonatal periods or in adulthood. 第三项研究（研究者：唐纳德·雷尼（Donald Rainnie），博士学位和保罗·普洛茨基（Paul M. Plotsky），博士学位）将通过评估早期生活压力如何改变质状末端（BNST）床核中信号的平衡来解决重要的功能问题，从而使压力诱导的5-HT输入到该区域对刺激的抗压剂抑制了抑制型刺激​​的可能性，从而抑制了抑制型抑制型抑制。第四项研究（研究人员：M。MarSanchez，PhD和Paul M. Plotsky，PhD）将开始对我们现有同伙的恒河猴猴子大脑采样的基因表达和受体结合后的验尸分析（请参阅Conte Monkey Core 9003）。总之，这些成分对大鼠和恒河类模型中神经环节的长期胁迫的长期后果进行了多方面的研究。这些数据对于比较和解释人类研究中获得的成像数据很重要。此外，它们可能具有重要的理论意义和临床意义。优秀动物模型，复杂的科学问题，最先进的技术以及该项目参与者之间的非凡专业知识的融合使我们能够以系统的方式解决早期生活压力如何影响所选神经电路以及随后的行为和神经内脏的问题。