Physiological Functions of Neuropeptide S

神经肽S的生理功能

• 批准号: 7051384
• 负责人: RAINER K REINSCHEID
• 金额: $ 28.89万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-08 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7051384
• 关键词: anxiety; arousal; asthma; attention deficit disorder; behavior test; behavioral /social science research tag; circadian rhythms; electroencephalography; gene expression; gene targeting; genetically modified animals; human tissue; in situ hybridization; laboratory mouse; laboratory rat; locus coeruleus; neural transmission; neuropeptide receptor; neuropeptides; neuropharmacology; neurotransmitter transport; psychophysiology; sleep; stress; wakefulness

DESCRIPTION (provided by applicant): We have identified a novel neuropeptide, termed NPS, that is predominantly expressed in a cluster of previously unidentified neurons in close vicinity to the noradrenergic locus coeruleus. The locus coeruleus is a brainstem structure involved in regulating sleep-wake cycles, arousal, attention and stress. Dysfunction of this brain area has been implicated in a number of disorders such as insomnia, narcolepsy and attention deficit hyperactivity disorder. More widespread expression of the NPS receptor is found in several brain areas, including cortex, thalamus and hypothalamus. Our preliminary results show that NPS promotes arousal when injected in mice. NPS also induces wakefulness while suppressing REM sleep and deep sleep in rats. Furthermore, NPS appears to produce anxiolytic-like effects. Therefore, NPS could represent a new transmitter system involved in neuronal modulation of vigilance and stress. We propose to study in detail the anatomical distribution of this novel transmitter system and the pharmacology of its receptor. We will determine the coexistence of NPS with known transmitters and its effect on the release of other transmitters involved in arousal. Furthermore, we will investigate its role in sleep and wakefulness and a possible involvement in attention and anxiety. Since no antagonist to the NPS receptor is currently available, we propose a genetic approach to delete the NPS gene in mice and study the behavioral consequences of NPS deficiency. Together, these studies will lay the foundation for understanding the physiological functions of NPS which may also yield new insights into human psychiatric disorders. A mutation in the human NPS receptor was recently found to be associated with increased risk of asthma. We will study the pharmacology of the mutant receptor isoforms which may help to understand the physiological consequences of the mutation in human airway tissue.

描述（由申请人提供）：我们已经鉴定出一种新型神经肽，称为 NPS，其主要在靠近去甲肾上腺素能蓝斑的一组先前未鉴定的神经元中表达。蓝斑是一种脑干结构，参与调节睡眠-觉醒周期、觉醒、注意力和压力。该大脑区域的功能障碍与许多疾病有关，例如失眠、嗜睡症和注意力缺陷多动障碍。 NPS 受体在多个大脑区域有更广泛的表达，包括皮质、丘脑和下丘脑。我们的初步结果表明，NPS 注射到小鼠体内后会促进兴奋。 NPS 还可以诱导大鼠觉醒，同时抑制快速眼动睡眠和深度睡眠。此外，NPS 似乎能产生类似抗焦虑的作用。因此，NPS 可以代表一种新的神经递质系统，参与警觉和压力的神经元调节。我们建议详细研究这种新型递质系统的解剖分布及其受体的药理学。我们将确定 NPS 与已知递质的共存情况及其对参与唤醒的其他递质的释放的影响。此外，我们将研究它在睡眠和觉醒中的作用以及可能与注意力和焦虑有关的作用。由于目前尚无 NPS 受体拮抗剂，我们提出了一种遗传方法来删除小鼠中的 NPS 基因，并研究 NPS 缺乏的行为后果。总之，这些研究将为理解 NPS 的生理功能奠定基础，这也可能对人类精神疾病产生新的见解。最近发现人类 NPS 受体的突变与哮喘风险增加有关。我们将研究突变受体亚型的药理学，这可能有助于了解人类气道组织突变的生理后果。