The Role Leptin on Arousal

瘦素在性唤起中的作用

• 批准号: 8329195
• 负责人: Paige B. Beck
• 金额: $ 3.02万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8329195
• 关键词: 6-Cyano-7-nitroquinoxaline-2,3-dione; Address; Affect; Agonist; Animals; Anxiety Disorders; Area; Arousal; Auditory; Biological; Bipolar Disorder; Body Weight; Brain Stem; Brain region; Carbachol; Cell Nucleus; Cells; Cholinergic Receptors; Controlled Study; Coupled; Coupling; Desire for food; Disease; Electric Stimulation; Elements; Evoked Potentials; Gap Junctions; Glutamate Receptor; Glutamates; Hormones; Hypothalamic structure; In Vitro; Individual; Injection of therapeutic agent; Leptin; Life; Locomotion; Measures; Membrane; Membrane Potentials; Mental disorders; Metabolic Pathway; Methods; Modafinil; Muscle Tonus; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; NMDA receptor antagonist; Narcolepsy; Neurons; Neurosciences Research; Obesity; Output; Pathway interactions; Population; Publishing; REM Sleep; Rattus; Reproduction; Research Design; Rest; Role; Schizophrenia; Sleep; Sleep Disorders; Slow-Wave Sleep; System; Technical Expertise; Techniques; Testing; Thalamic structure; Time; Wakefulness; arm; cholinergic; clinically relevant; indexing; nervous system disorder; neuropsychiatry; patch clamp; receptor; research study; response; sleep regulation; translational neuroscience; transmission process

DESCRIPTION (provided by applicant): Dysregulation of sleep/wake control can result in life-long disturbances in arousal and REM sleep drive, leading to hypervigilance or hypovigilance such as that observed in a number of neuropsychiatric disorders such as schizophrenia, anxiety disorder, bipolar disorder, and narcolepsy. Study of the control of sleep and waking has the potential for making a major impact on a number of disorders, making translational neuroscience research on this area critical. One element of the reticular activating system (RAS) is the pedunculopontine nucleus (PPN), which is the cholinergic arm of the RAS, and projects to the thalamus to trigger thalamocortical rhythms, and to the brainstem to modulate muscle tone and locomotion. Leptin is an adipokine that regulates appetite, body weight, and reproduction by way of receptors in the hypothalamus. The hormone also has receptors in various other regions of the brain, including the PPN. While leptin is known to be an active regulator in the hypothalamus, the hormone's role in the PPN (and thus in wakefulness) is not established. It has been shown that leptin levels are decreased in individuals with obesity, who also have sleep dysregulation. Studies have shown that leptin significantly decreases the duration of REM sleep and increases the duration of slow wave sleep. The proposed experiment will entail testing the effect of leptin on the PPN in single cells, populations of cells, and in the whole animal. This will be established by performing whole-cell patch clamp and population response recordings in vitro, and by recording the sleep state-dependent auditory P13 evoked potential in freely moving rats, a measure of level of arousal that is generated by the PPN. After determining the effects of leptin using these three techniques, the biological mechanisms by which leptin acts will be determined by performing single cell recordings using several intracellular pathway blockers. This project will lay out the role of leptin in sleep-wake control from the single cell all the way up to the whole animal. This experiment is clinically important because, by determining the role of leptin in the PPN and, therefore, sleep and waking, the potential role of leptin in sleep disorders and perhaps a number of psychiatric and neurological disorders will also be determined.

描述（由申请人提供）：睡眠/尾流控制失调可能会导致唤醒和REM睡眠驱动器的终生障碍，导致过度耐药性或不足性，例如在许多神经精神疾病中观察到的，例如精神分裂症，焦虑症，双相情感障碍，双相情感障碍和麻醉症。对睡眠和醒来的控制的研究有可能对多种疾病产生重大影响，从而使对该领域的转化神经科学研究至关重要。网状激活系统（RAS）的一个要素是Pedunculopontine核（PPN），该核是Ras的胆碱能臂，并向丘脑投射以触发丘脑皮质节律，并向脑干触发脑干以调节肌肉张力和肌肉张力。 瘦素是一种脂肪因子，可通过下丘脑中的受体调节食欲，体重和繁殖。激素在包括PPN在内的大脑其他各个区域也具有受体。尽管已知瘦素是下丘脑中的活性调节剂，但尚未确定激素在PPN中的作用（因此在觉醒中）。已经表明，肥胖患者的瘦素水平也降低，患有睡眠失调。研究表明，瘦素显着降低了REM睡眠的持续时间，并增加了慢波睡眠的持续时间。提出的实验将需要测试瘦素对单个细胞，细胞种群和整个动物中PPN的影响。这将通过在体外进行全细胞贴片夹和种群响应记录来确定，并记录睡眠状态依赖性的听觉p13引起了自由移动大鼠的潜力，这是PPN产生的一种唤醒水平的度量。在使用这三种技术确定瘦素的作用后，将通过使用几个细胞内途径阻滞剂进行单细胞记录来确定瘦素作用的生物学机制。 该项目将列出瘦素在从单个细胞到整个动物的单个细胞中的睡眠效果控制中的作用。该实验在临床上很重要，因为通过确定瘦素在PPN中的作用，因此，瘦素在睡眠障碍中的潜在作用以及可能的许多精神病和神经系统疾病也将得到确定。