DOPAMINE-NEUROPEPTIDE COEXISTENCE AND MENTAL FUNCTION

该项目是为精神健康领域的神经科学工作组而设计的 将在纽约大学医学中心进行 卡罗林斯卡研究所，并将调查 中枢神经系统中的多巴胺能和肽能神经系统 生理和病理状态。解剖学、生物化学 而多巴胺(DA)神经元的生理异质性将 被研究。免疫组织化学结合原位 杂交和逆行示踪，将用于研究 多巴胺及其特异体的定位和细胞分化 神经肽，以及非递质蛋白。这三个人 程序代表着互补的方法论，而且远不止 组合在一起比任何一个人都强大。的共地化 DA与其他递质和非递质物质将 识别不同的DA神经元亚群，并可作为标记 对于特定的DA神经元亚群，这些神经元共享某些调控 机械装置。将有可能定量地确定 不同DA患者酪氨酸羟化酶(TH)基因表达的差异 并定义TH在不同种群中的表达率 中脑DA细胞与共存多肽的关系。这个 急性和慢性抗精神病药物的反应性差异 治疗可能归因于自身受体的密度 调节不同前脑DA的合成和/或释放 DA神经支配。因此，可以定义不同的 中脑多巴胺能神经元的群数 D2DA受体结合部位的免疫组织化学染色。 此外，参与脱敏的机制还包括 不同的DA受体亚型将被研究，偶联 D1DA受体结合蛋白与腺苷环化酶之间的关系 死后非精神分裂症患者和精神分裂症患者的大脑 学习。

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.