Physiological Functions of Neuropeptide S

神经肽S的生理功能

• 批准号: 7208998
• 负责人: RAINER K REINSCHEID
• 金额: $ 27.99万
• 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/7208998
• 关键词: Acetylcholine; Amygdaloid structure; Anti-Anxiety Agents; Anxiety; Area; Arousal; Asthma; Attention; Attention deficit hyperactivity disorder; Autoradiography; Behavior; Behavioral; Brain; Brain Stem; Cell Nucleus; Circadian Rhythms; Collaborations; Communication; Data; Depth; Development; Disease; Dopamine; Electroencephalography; Emotional; Event; Foundations; Functional disorder; Gene Targeting; Genes; Genetic; Genetic Recombination; Glutamates; Histamine; Human; Hypersensitivity; Hypothalamic structure; Immune Sera; In Situ; In Situ Hybridization; In Vitro; Investigation; Knock-out; Knowledge; Letters; Ligands; Link; Locomotion; Maps; Measures; Mental disorders; Messenger RNA; Monitor; Mus; Mutation; Narcolepsy; Neurons; Neuropeptides; Neurotransmitters; Norepinephrine; Numbers; Pathway interactions; Peptides; Peripheral; Pharmacology; Phenotype; Physiological; Point Mutation; Polymerase Chain Reaction; Protein Isoforms; REM Sleep; RNA Splicing; Rattus; Regulation; Research Personnel; Resolution; Risk; Role; Second Messenger Systems; Serotonin; Signal Transduction; Sleep; Sleep Architecture; Sleep Wake Cycle; Sleeplessness; Stimulus; Stress; Structure; System; Thalamic structure; Tissues; Wakefulness; base; biological adaptation to stress; gamma-Aminobutyric Acid; human tissue; in vivo; insight; locus ceruleus structure; memory process; mutant; neurochemistry; noradrenergic; novel; programs; receptor; second messenger; sleep regulation; stable cell line; vigilance

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）：我们已经确定了一种新型的神经肽，称为NP，该神经肽主要在与去甲肾上腺素能基因座近附近的先前未识别的神经元集群中表达。基因座层是一种脑干结构，涉及调节睡眠效果周期，唤醒，注意力和压力。该大脑区域的功能障碍与多种疾病有关，例如失眠，睡病和注意力缺陷多动障碍。在包括皮质，丘脑和下丘脑在内的几个大脑区域中发现了NPS受体的更广泛的表达。我们的初步结果表明，在小鼠中注射时NP会促进唤醒。 NP还会引起清醒，同时抑制大鼠的REM睡眠和深度睡眠。此外，NP似乎会产生类似抗焦虑的作用。因此，NP可以代表参与警惕和压力神经元调节的新发射器系统。我们建议详细研究这种新型发射机系统及其受体药理学的解剖分布。我们将确定NP与已知发射器的共存及其对涉及唤醒的其他发射器的释放的影响。此外，我们将调查其在睡眠和清醒中的作用，并可能参与注意力和焦虑。由于目前没有对NPS受体的拮抗剂，因此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。这些研究将共同​​理解NP的生理功能，从而为人类精神疾病提供新的见解。最近发现人NPS受体中的突变与哮喘的风险增加有关。我们将研究突变受体同工型的药理学，这可能有助于了解人气道组织突变的生理后果。