DOPAMINE-NEUROPEPTIDE COEXISTENCE AND MENTAL FUNCTION

多巴胺-神经肽共存和心理功能

基本信息

批准号：
3099084
负责人：
EMANUEL MELLER
金额：
$ 43.15万
依托单位：
NEW YORK UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-01-01 至 1993-12-31
项目状态：
已结题

项目摘要

This program project for Neuroscience Work Groups in Mental Health will be carried out at New York University Medical Center and Karolinska Institute, Stockholm, and will investigate the role of dopaminergic and peptidergic neuronal systems in CNS function in physiological and pathological states. The anatomical, biochemical and physiological heterogeneities of the dopamine (DA) neurons will be studied. Immunohistochemistry, in combination with in situ hybridization and retrograde tracing, will be used for studies on localization and cellular differentiation of DA and specific neuropeptides, as well nontransmitter proteins. These three procedures represent complementary methodology and are much more powerful in combination than any one alone. The colocalization of DA with other transmitter and nontransmitter substances will identify distinct subsets of DA neurons, and may serve as a marker for specific subsets of DA neurons which share certain regulatory mechanisms. It will be possible to quantitatively establish differences in tyrosine hydroxylase (TH) mRNA in different DA populations and define the rate of expression of TH in different midbrain DA cells in relation to coexistent peptides. The differences in responsiveness to acute and chronic neuroleptic treatment may be attributable to the density of autoreceptors regulating synthesis and/or release of DA in different forebrain DA innervation. It may therefore be possible to define distinct populations of midbrain DA neurons on the basis of immunohistochemical staining for the D2 DA receptor binding sites. Furthermore, the mechanisms involved in the desensitization of various DA receptor subtypes will be investigated and the coupling between D1 DA receptor binding protein and adenylate cyclase in postmortem non-schizophrenic and schizophrenic brain will be studied.

这个针对心理健康神经科学工作组的计划项目将在纽约大学医学中心和斯德哥尔摩的Karolinska研究所，并将调查中枢神经系统功能中的多巴胺能和替代性神经元系统生理和病理状态。解剖学，生化多巴胺（DA）神经元的生理异质性将被研究。免疫组织化学与原位结合杂交和逆行追踪将用于研究 DA和特定的定位和细胞分化神经肽以及非转移蛋白。这三个程序代表互补方法，更多组合比任何一个人都强大。共定位具有其他发射器和非发送器物质的DA将会识别DA神经元的不同子集，可以用作标记对于具有某些调节的DA神经元的特定子集机制。可以定量建立不同DA中酪氨酸羟化酶（Th）mRNA的差异种群并定义了不同的表达速率中脑DA细胞与共存的肽有关。这对急性和慢性神经疗法的反应性差异治疗可能归因于自身受体的密度调节不同前脑中DA的合成和/或释放 DA神经。因此，可以定义不同的基于 D2 DA受体结合位点的免疫组织化学染色。此外，脱敏的机制将研究各种DA受体亚型和耦合在D1 DA受体结合蛋白和腺苷酸环化酶之间验尸非雪人和精神分裂症大脑将是研究。

项目成果

期刊论文数量（73）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Neuropeptide Y and catecholamine synthesizing enzymes and their mRNAs in rat sympathetic neurons and adrenal glands: studies on expression, synthesis and axonal transport after pharmacological and experimental manipulations using hybridization techniques

大鼠交感神经元和肾上腺中的神经肽 Y 和儿茶酚胺合成酶及其 mRNA：使用杂交技术进行药理学和实验操作后的表达、合成和轴突运输的研究

DOI：
10.1016/0306-4522(91)90365-u
发表时间：
1991
期刊：
Neuroscience
影响因子：
3.3
作者：
Schalling,M;Franco-Cereceda,A;Hemsén,A;Dagerlind,A;Seroogy,K;Persson,H;Hökfelt,T;Lundberg,JM
通讯作者：
Lundberg,JM

Further analysis of presence of peptides in dopamine neurons. Cholecystokinin, peptide histidine-isoleucine/vasoactive intestinal polypeptide and substance P in rat supramammillary region and mesencephalon.

进一步分析多巴胺神经元中肽的存在。