Conte Centers for the Neuroscience of Depression

孔特抑郁症神经科学中心

• 批准号: 8063247
• 负责人: RANGA R KRISHNAN
• 金额: $ 42.16万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8063247
• 关键词: Biology; Brain; Cell Count; Cognitive; Depressive disorder; Disease; Ensure; Functional Magnetic Resonance Imaging; Glutamates; Knockout Mice; Lesion; Mental Depression; Neurons; Neurosciences; Norepinephrine; Pattern; Research; Resource Sharing; Resources; Role; Serotonin; Transgenic Mice; Transgenic Organisms; cell type; data management; design; improved; monoamine; neurobiological mechanism; serotonin receptor; statistics; technological innovation; white matter

Description (Provided by Applicant): The proposed Silvio O. Conte Center for Neuroscience of Depression will focus on understanding the neurobiological mechanism of depression. A total of 5 projects are proposed. The center is focused on a single hypothesis. The first project examines localization of lesions, structural changes in critical regions subserving the circuit, alterations in the white matter tracts relevant to the circuit and changes in glutamate. The second project uses post mortem cell counting and cellular localization in serotonin receptors and assessment of the type of cell loss in the orbitofrontal cortex. The third project uses cognitive paradigms and functional MRI to probe the circuit and the role of brain lesions and serotonin on the functioning of this circuit. The fourth project uses transgenic and knockout mice to examine to role of norepinephrine and serotonin as it relates to the circuit. The final project is designed to assess in these transgenic mice using multielectrode array of single neuron recordings of the firing pattern of the circuit neurons in various states and tasks and the role of monoamines in modulating this circuit. Three shared resources, administrative, research and assessment and data management/statistics are proposed to facilitate the conduct of these projects and to ensure integration at the conceptual, analytical and resource availability level, and flow to the various projects. Findings from the center should greatly enhance our understanding of the biology of depressive disorders and help improve the treatment of these disorders. In addition, the technological innovations developed in the context of this project are likely to be of major importance and relevant to other studies of brain function.

描述（申请人提供）： Silvio O. Conte抑郁症神经科学中心将专注于了解抑郁症的神经生物学机制。共提出5个项目。该中心专注于一个单一的假设。第一个项目检查局部病变，结构变化的关键领域subserving电路，改变在白色物质束相关的电路和谷氨酸的变化。第二个项目使用死后细胞计数和5-羟色胺受体的细胞定位，并评估眶额皮质细胞损失的类型。第三个项目使用认知范式和功能性MRI来探测电路以及大脑病变和血清素对该电路功能的作用。第四个项目使用转基因和基因敲除小鼠来检查去甲肾上腺素和5-羟色胺在回路中的作用。最后一个项目的目的是评估在这些转基因小鼠中使用多电极阵列的单神经元记录的放电模式的电路神经元在各种状态和任务和单胺在调制这个电路的作用。建议共享三种资源：行政、研究和评估以及数据管理/统计，以促进这些项目的开展，并确保在概念、分析和资源可得性方面实现一体化，并流向各个项目。该中心的发现将极大地增强我们对抑郁症生物学的理解，并有助于改善这些疾病的治疗。此外，在该项目背景下开发的技术创新可能具有重大意义，并与其他大脑功能研究相关。

项目成果

Cortical-amygdalar circuit dysfunction in a genetic mouse model of serotonin deficiency.

• DOI: 10.1523/jneurosci.4891-12.2013
• 发表时间: 2013-03-06
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Dzirasa K;Kumar S;Sachs BD;Caron MG;Nicolelis MA
• 通讯作者: Nicolelis MA

Knockout of the norepinephrine transporter and pharmacologically diverse antidepressants prevent behavioral and brain neurotrophin alterations in two chronic stress models of depression.

在两个慢性抑郁症模型中，去甲肾上腺素转运蛋白和药理学多样的抗抑郁药的敲除可以防止行为和脑神经营养蛋白改变。

• DOI: 10.1111/j.1471-4159.2009.06345.x
• 发表时间: 2009-10
• 期刊: Journal of neurochemistry
• 影响因子: 4.7
• 作者: Haenisch B;Bilkei-Gorzo A;Caron MG;Bönisch H
• 通讯作者: Bönisch H

Reduced level of glutamic acid decarboxylase-67 kDa in the prefrontal cortex in major depression.

• DOI: 10.1017/s1461145709990587
• 发表时间: 2010-05
• 期刊: The international journal of neuropsychopharmacology
• 作者: Karolewicz B;Maciag D;O'Dwyer G;Stockmeier CA;Feyissa AM;Rajkowska G
• 通讯作者: Rajkowska G

Serotonin deficiency alters susceptibility to the long-term consequences of adverse early life experience.

• DOI: 10.1016/j.psyneuen.2014.12.019
• 发表时间: 2015-03
• 期刊: PSYCHONEUROENDOCRINOLOGY
• 影响因子: 3.7
• 作者: Sachs, Benjamin D.;Rodriguiz, Ramona M.;Tran, Ha L.;Iyer, Akshita;Wetsel, William C.;Caron, Marc G.
• 通讯作者: Caron, Marc G.

AGTR1 gene variation: association with depression and frontotemporal morphology.

• DOI: 10.1016/j.pscychresns.2012.03.007
• 发表时间: 2012-05-31
• 期刊: Psychiatry research
• 影响因子: 11.3
• 作者: Taylor WD;Benjamin S;McQuoid DR;Payne ME;Krishnan RR;MacFall JR;Ashley-Koch A
• 通讯作者: Ashley-Koch A