SLEEP REGULATION--INVOLVEMENT OF GRF-LIKE PEPTIDES

本提案的主要目的是检验以下假设： 下丘脑GRF样肽参与睡眠 监管，即，生长激素释放因子 （血管活性肠肽）和PHI（肽组氨酸- 异亮氨酸）。 我们假设GRF刺激GH（生长 激素）分泌和促进非快速眼动睡眠（NREMS）， 下丘脑神经元的平行但可分离的功能 投射到正中隆起和基底前脑 催眠区 此外，GH和SOM（生长抑素）释放， GRF可以促进NREMS之后的REMS（REM睡眠）。 VIP和PHI 在结构上与GRF相关，并刺激 垂体催乳素（催乳素），可以通过 具体的运输机制。 假设VIP/PHI-PRL轴 对REMS有许可或促进作用。 一些以前 建议的睡眠因素，例如，白细胞介素-I（IL 1）可通过 这些内分泌机制。 这个假设是基于 初步数据和以前的报告：1）GH和PRL分泌 2）GRF首先促进NREMS，然后促进REMS， GH和SOM选择性地促进REMS; 3）VIP和PRL均增加 REMS;和4）建议的睡眠因素影响内分泌调节。 将通过研究GRF、VIP、 PHI和PRL对睡眠、体温调节和激素分泌的影响 在侧脑室、脑内、全身注射后。 抗GRF抗体与GRF神经元的药理学损伤 将被用来阻止内源性GRF行动，以确定作用 内源性GRF在生理睡眠和睡眠（和GH 分泌）。 内源性泌乳素的贡献， 生理睡眠和由VIP和PHI引起的REMS将是 在用PRL抗体预处理的动物中研究。 睡眠相关 将测量GRF分泌物的变化。 实验 将在长期植入 EEG电极、脑内插管和心内导管。 激素水平将通过ELISA或RIA测量， 系列样本 我们预计，结果将提供 证据表明内分泌和睡眠调节涉及共同的 调控途径。

The broad objective of this proposal is to examine the hypothesis that hypothalamic GRF-like peptides are involved in sleep regulation, i.e., GRF (growth hormone releasing factor), VlP (vasoactive intestinal peptide) and PHI (peptide histidine- isoleucine). We hypothesize that GRF stimulation of GH (growth hormone) secretion and promotion of nonREM sleep (NREMS) are parallel, albeit dissociable, functions of hypothalamic neurons which project to both the median eminence and basal forebrain hypnogenic areas. Further, GH and SOM (somatostatin) released by GRF may promote REMS (REM sleep) subsequent to NREMS. VlP and PHI are structurally related to GRF and stimulate secretion of pituitary PRL (prolactin) that can reach the brain by means of a specific transport mechanism. The VIP/PHI-PRL axis is assumed to have a permissive or facilitatory effect on REMS. Some previously proposed sleep factors, e.g., interleukin-l (ILl), may act through these endocrine mechanisms. The hypothesis is based upon preliminary data and previous reports: 1) GH and PRL secretions are coupled to sleep; 2) GRF promotes first NREMS then REMS, while GH and SOM selectively promote REMS; 3) both VIP and PRL increase REMS; and 4) proposed sleep factors affect endocrine regulation. The hypothesis will be tested by studying the effects of GRF, VIP, PHI, and PRL on sleep, thermoregulation and secretion of hormones after intracerebroventricular, intracerebral, systemic injection. Antibodies against GRF and pharmacological lesions of GRF neurons will be used to block endogenous GRF actions to determine the role of endogenous GRF in physiological sleep and in sleep (and GH secretion) elicited by ILl. The contribution of endogenous PRL to physiological sleep and to REMS elicited by VIP and PHI will be studied in animals pretreated with PRL antibodies. Sleep-related variations in GRF secretions will be measured. The experiments will be carried out in rats and rabbits chronically implanted with EEG electrodes, intracerebral cannulas and intracardial catheters. Hormone levels will be measured by means of ELISA or RIA from serial samples. We anticipate that the results will provide evidence that endocrine and sleep regulations involve common regulatory pathways.