PROTEIN NEUROTRANSMISSION AND BEHAVIOR

蛋白质神经递质参与启动和维持 哺乳动物的复杂行为。此外，蛋白质的异常 神经传递无疑会被发现是一些 神经精神疾病。研究异常的模型的发展 蛋白质神经传递及其与临床的相关性 然而，疾病由于缺乏临床或治疗方法而受到阻碍。 实验上有用的药物来改变蛋白质神经传递，并通过 缺乏临床方法来评估蛋白神经传递。 行为受到干扰。这项提议的目的有两个：第一， 多肽翻译后加工的基础研究 中枢神经系统中的神经递质；第二，寻找 行为和行为中蛋白质神经传递异常的证据 认知障碍。第一个项目将包括基础、生化 多肽的酰胺化、N-末端谷氨酰环化的研究 TRH加压因子的翻译后处理。这个项目是 与催化剂的分离、纯化、定义有关 机制、免疫细胞化学定位及生理学 催化这些翻译后反应的酶的调节 修改。这个项目的第三个方面，研究 TRH前体的翻译后处理，旨在用作 研究这些特殊神经元适应所需的模型 在远端神经中保持足够的蛋白质神经传递储存 终点站。第二个主要计划将决定一个 翻译后加工中的结构性缺陷或异常 可能与智力低下、情感障碍或精神错乱有关 无论是严重精神残疾的年轻人还是老年人 精神疾病。血清缩氨酸甘氨酸单加氧酶和 谷氨酰胺环转移酶将在这些类型的患者中进行测定 并与他们的临床疾病相关。 这项研究涉及的方法将包括高压液体 层析、放射免疫分析、抗血清、氨基酸的生成 分析、质谱学、免疫亲和层析、凝胶 层析，快速蛋白质液相色谱，等电聚焦， 薄层层析、固相和液态蛋白质合成 化学反应。

Protein neurotransmitters are involved in initiating and maintaining complex behaviors in mammals. Furthermore, abnormalities of protein neurotransmission will undoubtedly be found to underlie some neuropsychiatric illness. The development of models to study abnormal protein neurotransmission and the correlation of these models with clinical disease, however, has been impeded by the lack of clinically or experimentally useful drugs to modify protein neurotransmission and by the lack of clinical methods to evaluate protein neurotransmission in the behaviorally disturbed. The purpose of this proposal is two-fold: First, basic investigations into posttranslational processing of peptide neurotransmitters in the central nervous system; and second, a search for evidence of abnormal protein neurotransmission in the behaviorally and cognitively disabled. The first project will include basic, biochemical studies of peptide amidation, N-terminal glutaminyl cyclization, and the posttranslational processing of the presursor for TRH. This project is concerned with isolation, purification, definition of the catalytic mechanisms, immunocytochemical localization and the physiological regulation of the enzymes catalyzing these posttranslational modifications. The third aspect of this project, studies of the posttranslational processing of TRH precursor, is intended to serve as a model for studies of those special neuronal adaptations required to maintain adequate stores of protein neurotransmission in distal nerve terminals. The second major program will determine whether a constitutional deficiency or abnormality in posttranslational processing may be associated with mental retardation, affective disorder or psychosis in young and old adults who are either severely mentally disabled or psychiatrically ill. Serum levels of peptidyl glycine monooxygenase and glutamine cyclotransferase will be determined in these types of patients and correlated with their clinical illness. Methods involved in this research will include high pressure liquid chromatography, radioimmunoassay, generation of antisera, amino acid analysis, mass spectroscopy, immunoaffinity chromatography, gel chromatography, fast protein liquid chromatography, isoelectric focusing, thin layer chromatography, and solid phase and liquid protein synthetic chemistry.