ROLE OF GABAERGIC NEURONS IN AUTONOMIC NUCLEI

伽巴能神经元在自主核中的作用

• 批准号: 3476985
• 负责人: BANG H HWANG
• 金额: $ 5.77万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3476985
• 关键词: GABA receptor; aminoacid inhibitor; autonomic disorder; autoradiography; benzodiazepine receptor; benzodiazepines; bicuculline; cardiovascular pharmacology; central neural pathway /tract; experimental brain lesion; gamma aminobutyrate; high performance liquid chromatography; histochemistry /cytochemistry; hypertension; hypothalamus; immunocytochemistry; in situ hybridization; innervation; laboratory rat; neuroendocrine system; neurotoxins; neurotransmitter metabolism; pituitary gonadal axis; radioimmunoassay; radiotracer; solitary tract nucleus; spontaneous hypertensive rat; vasopressins

Gamma aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the brain. Central administration of GABA and its agonists lowers blood pressure, but it is little known as to which and how GABA systems are involved in the cardiovascular regulation. The primary goal of this proposal is to elucidate the role of GABAergic neurons in regulation of the vasopressin (VP) neurons in (a) the paraventricular hypothalamic nucleus (PVN) - nucleus tractus solitarius (NTS) autonomic pathway, and (b) the PVN - pituitary neuroendocrine axis. However, my long-term objective is to study mechanisms by which central GABAergic neurons modulate blood pressure. Electron microscopic immunocytochemistry, high performance liquid chromatography, radiometric assay (for glutamate decarboxylase, GAD), radioimmunoassay (for detecting VP contents), in situ hybridization (for studying VP mRNA), and quantitative receptor autoradiography will be applied to evaluate the GABA and VP neurons of spontaneously hypertensive (SHR) rats. More specifically, this proposal is: 1) to reveal GABAergic neurons supplying the PVN, lateral "circumventricular" region (LCV), and NTS; 2) to characterize GAD activities, GABA synaptogenesis, GABA contents, GABA turnover and GABA receptors in the PVN, LCV, and NTS of SHR rats; 3) to evaluate the relationship between GABA parameters and VP parameters (i.e., VP mRNA and VP contents) in the PVN; 4) to study whether receptors for benzodiazepines (which are closely interacted with endogenous GABA), are in conjunction with GABA receptors to associate with hypertension; 5) to determine whether and how changes of GABA/VP parameters in the PVN are correlated with GABA/VP parameters in the NTS during the development of hypertension; and 6) to verify that there are functional GABA receptors in the PVN to regulate VP, by studying VP contents in the NTS, pituitary and plasma after microinjections of a GABA antagonist into the PVN. These studies may provide new information on the neural basis of hypertension associated with GABA/VP neurons, which will be useful for drug developments aimed at the treatment or prevention of hypertension.

γ-氨基丁酸 (GABA) 是一种主要的抑制剂 大脑中的神经递质。 GABA 中央管理 及其激动剂可以降低血压，但鲜为人知的是 GABA 系统参与心血管疾病以及如何参与 规定。 该提案的主要目标是阐明 GABA 能神经元在加压素 (VP) 调节中的作用 (a) 下丘脑室旁核 (PVN) 中的神经元 - 孤束核 (NTS) 自主神经通路，以及 (b) PVN-垂体神经内分泌轴。 然而，我的长期 目的是研究中枢 GABA 能的机制 神经元调节血压。 电镜免疫细胞化学，高性能 液相色谱法、放射测定法（谷氨酸 脱羧酶、GAD）、放射免疫分析（用于检测VP 内容），原位杂交（用于研究 VP mRNA），以及 定量受体放射自显影将用于评估 自发性高血压 (SHR) 的 GABA 和 VP 神经元 老鼠。 更具体地说，该提案是：1）揭示GABAergic 供应 PVN、外侧“室周”区域的神经元 (LCV) 和 NTS； 2）表征GAD活动，GABA 突触发生、GABA 含量、GABA 周转和 GABA SHR 大鼠 PVN、LCV 和 NTS 中的受体； 3）评估 GABA参数与VP参数的关系 PVN 中的（即 VP mRNA 和 VP 含量）； 4）研究是否 苯二氮卓类受体（与 内源性 GABA），与 GABA 受体结合 与高血压有关； 5）确定是否以及如何 PVN 中 GABA/VP 参数的变化与 开发过程中 NTS 中的 GABA/VP 参数 高血压; 6) 验证是否存在功能性 GABA 通过研究PVN中的VP含量来调节VP 显微注射 GABA 后的 NTS、垂体和血浆 拮抗剂进入PVN。 这些研究可能提供有关神经基础的新信息 高血压与 GABA/VP 神经元相关，这将是 可用于旨在治疗或治疗的药物开发 预防高血压。