BRAIN NORADRENERGIC NEURONS, PEPTIDES AND STRESS
大脑去甲肾上腺素能神经元、肽和压力
基本信息
- 批准号:6343702
- 负责人:
- 金额:$ 25.98万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-01-01 至 2002-09-18
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (Adapted from applicant's abstract): This is a competitive
renewal of a proposal that was designed to test the guiding hypothesis that
the stress-related neurohormone, corticotropin-releasing hormone (CRH),
serves as a neurotransmitter to activate the major brain noradrenergic
nucleus, locus coeruleus (LC) during stress. Our previous studies provided
anatomical and physiological evidence supporting this hypothesis.
Additionally, these studies suggested certain circuits by which endogenous
CRH activates the LC, and certain physiological consequences of this
activation. The following AIMS extend these previous studies: Aim 1 will
characterize the anatomical substrates underlying CRH regulation of the LC
at an ultrastructural level using electron microscopy and dual labeling
immunohistochemistry. It will be determined whether CRH terminals directly
contact LC cells and/or LC dendrites that extend into the pericoerulear
region, or terminals of other afferents to the LC. Sources of CRH inputs to
the LC and pericoerulear region will be confirmed using electron microscopy
and double labeling of terminals for CRH and anterograde tract tracers.
This approach will also be used to identify other LC afferents that CRH may
interact with. Aim 2 will identify specific CRH systems that regulate LC
activity during different types of stress. The impact of activating
identified CRH afferents to the LC or pericoeulear region on LC discharge
will be characterized, and the role of neurotransmitter CRH in these effects
will be determined. By combining retrograde tract tracing from the LC with
immunohistochemistry for CRH and immediate early gene proteins, CRH
afferents to the LC that are activated by specific stressors will be
identified. Aim 3 will test the hypothesis that a consequence of LC
activation by endogenous CRH during stress is suppression of cell-mediated
immunity. The effects of CRH microinfusion into the LC on spleen
T-lymphocyte mitogenic activity will be quantified and the role of
stress-elicited CRH release in the LC in suppression of cell-mediated
immunity will be determined. Taken together, these Aims examine the CRH-LC
connection in stress at both an input (ultrastructural and systems level)
and an output (functional) level. CRH-brain noradrenergic interactions are
thought to be involved in adaptive and pathological consequences of stress.
As stress is thought to be a major contributing factor to a number of
psychiatric disorders, these studies will facilitate our understanding of
the etiology of stress-related psychiatric disorders, their treatment and
prevention.
描述(改编自申请人的摘要):这是一个竞争性的
重新提出一项旨在检验指导假设的建议,
应激相关的神经激素,促肾上腺皮质激素释放激素(CRH),
作为一种神经递质激活大脑中主要的去甲肾上腺素能
核,蓝斑(LC)在应力。 我们之前的研究提供了
解剖学和生理学证据支持这一假设。
此外,这些研究表明,某些回路,
CRH激活LC,其某些生理后果
activation. 以下目标扩展了这些先前的研究:目标1将
表征LC CRH调节的解剖学基础
在超微结构水平上,使用电子显微镜和双标记
免疫组化 将确定CRH终端是否直接
接触LC细胞和/或LC树突,其延伸到红细胞周围。
区域,或其他传入LC的终端。 CRH输入的来源,
将使用电子显微镜证实LC和红细胞周围区域
CRH和顺行束示踪剂的终末双重标记。
这种方法也将用于识别CRH可能引起的其他LC传入。
互动。 目标2将确定规范LC的特定CRH系统
在不同类型的压力下活动。 激活的影响
确定CRH传入LC或周围脑区LC放电
将被描述,神经递质CRH在这些效应中的作用
将被确定。 通过将LC的逆行追踪与
CRH和即刻早期基因蛋白免疫组化
由特定压力源激活的LC传入神经将被激活,
鉴定 目标3将检验假设,即LC的后果
应激时内源性CRH的激活抑制了细胞介导的
免疫力 LC内微量输注CRH对脾脏的影响
T淋巴细胞促有丝分裂活性将被量化,
应激诱导的LC中CRH释放抑制细胞介导的
将确定豁免权。 综上所述,这些目标检查CRH-LC
在输入(超微结构和系统水平)的应力连接
和输出(功能)电平。 CRH-脑去甲肾上腺素能相互作用是
被认为与压力的适应性和病理性后果有关。
由于压力被认为是一个主要的因素,以一些
这些研究将有助于我们了解
与压力有关的精神障碍的病因、治疗和
预防
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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RITA VALENTINO其他文献
RITA VALENTINO的其他文献
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{{ truncateString('RITA VALENTINO', 18)}}的其他基金
Bladder Regulation by Corticotropin-Releasing Factor
促肾上腺皮质激素释放因子对膀胱的调节
- 批准号:
6964946 - 财政年份:2005
- 资助金额:
$ 25.98万 - 项目类别:
Bladder Regulation by Corticotropin-Releasing Factor
促肾上腺皮质激素释放因子对膀胱的调节
- 批准号:
7140376 - 财政年份:2005
- 资助金额:
$ 25.98万 - 项目类别:
CORTICOTROPIN RELEASING FACTOR/SEROTONERGIC INTERACTIONS
促肾上腺皮质激素释放因子/血清素相互作用
- 批准号:
2757947 - 财政年份:1998
- 资助金额:
$ 25.98万 - 项目类别:
CORTICOTROPIN-RELEASING FACTOR-SEROTONIN INTERACTIONS
促肾上腺皮质激素释放因子-血清素相互作用
- 批准号:
6994444 - 财政年份:1998
- 资助金额:
$ 25.98万 - 项目类别:
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