SLEEP DISORDERED BREATHING IN AGING ZUCKER RATS

老年 Zucker 大鼠的睡眠呼吸紊乱

• 批准号: 2706012
• 负责人: GASPAR Andrew FARKAS
• 金额: $ 7.43万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2706012
• 关键词: REM sleep; aging; biological models; body temperature; electromyography; laboratory rat; longitudinal animal study; obesity; oxygen consumption; pathologic process; polysomnography; respiratory airflow disorder; sleep apnea; sleep disorders; statistics /biometry; wakefulness

Changes in sleep and sleep quality in late life have implications for quality of life, level of functioning, and ability to remain independent. Complaints in initiating and maintaining sleep and of daytime drowsiness are among the most common health problems in the elderly. Sleep disordered breathing (SDB) is prevalent in the elderly and associated with severe and often life-threatening complications. Although the clinical features of SDB have been well described, the sequence of events and mechanisms responsible for initial increases in airway resistance or subsequent age associated devolution of the upper airway toward full occlusion (obstructive sleep apnea, OSA) remain unknown. Although it has been speculated that mild forms of SDB (upper airway resistance syndrome with snoring) and OSA represent the two extremes of a continuum of the same disorder, central and peripheral mechanisms that contribute to or enhance movement along this continuum are not fully understood. Because of the slow progression of SDB in humans, and the fact that most clinical studies have had to revert to a cross-sectional design, contributing factors associated with SDB in an aging population have proved difficult to delineate. Unquestionably, a suitable animal model that shares many of the same characteristics as noted in human SDB would be of tremendous value in determining consequential mechanisms responsible for the evolution of SDB in the aging population. The Zucker (Z.) Rat, an autosomal genetic model of obesity, offers many advantages as a model for studying the evolution of SDB: obese animals are not born obese, but develop the increased body mass as a function of age; a relatively short life-span (18 months) is ideal for inclusion of longitudinal studies to correlate specific mechanisms with age related dysfunction; the Z. Rat is very well defined as attested by the vast number of studies employing this model since its original description in 1961; the size is ideal to perform numerous perturbations and to study influences originating from secondary factors; obese Z. Rats present many of the same functional, central, and sleep state abnormalities as observed in humans with SDB; and lean litter-mates are available to serve as age- matched controls. The major hypothesis to be tested is that SDB naturally evolves in aging obese Z. rats and such this model will prove most advantageous in detecting mechanisms associated with the evolution of SDB. Only after these contributing mechanisms are fully understood can effective early interventions be contemplated.

晚年睡眠和睡眠质量的变化对 生活质量、功能水平和保持的能力 独立自主。在启动和维持睡眠方面的投诉以及 白天昏昏欲睡是最常见的健康问题之一 老年人。睡眠呼吸障碍(SDB)在老年人中普遍存在 老年人，并与严重的，往往危及生命的 并发症。尽管SDB的临床特征良好 所描述的事件序列和负责 与最初的呼吸道阻力增加或随后的年龄相关 上呼吸道向完全闭塞(阻塞性)方向松解 睡眠呼吸暂停，阻塞性睡眠呼吸暂停)仍不清楚。尽管有猜测说 轻度SDB(上呼吸道阻力综合征伴 打呼)和阻塞性睡眠呼吸暂停综合症代表了 同样的紊乱，中枢和外周机制导致 或增强沿这一连续体的运动还没有完全被理解。 因为SDB在人类中进展缓慢，而且事实是 大多数临床研究不得不恢复到横断面设计， 与老龄化人口中的SDB相关的促成因素有 事实证明很难描述。毫无疑问，一只合适的动物 一种与人类的许多特征相同的模型 SDB将在确定结果方面具有巨大的价值 SDB在衰老过程中演变的机制 人口。The Zucker(Z.)大鼠，一种常染色体的遗传模型 肥胖症作为研究进化的模型提供了许多优势 肥胖动物不是生来就肥胖，而是发展起来越来越胖 体重作为年龄的函数；相对较短的寿命(18 月)是包含纵向研究以进行关联的理想选择 年龄相关功能障碍的特定机制；Z.大鼠非常 大量的研究都证明了这一点 自1961年最初描述以来的型号；大小理想 进行多次扰动并研究产生的影响 来自次要因素；肥胖Z。大鼠表现出许多相同的 中观察到的功能、中枢和睡眠状态异常 患有SDB的人类和精瘦的产仔伴侣可以作为年龄- 配对的对照组。需要检验的主要假设是SDB 在衰老的肥胖Z.大鼠中自然进化，这样的模型将 事实证明，在检测与 SDB的演变。只有在这些促成机制完全 了解了这一点，就可以考虑进行有效的早期干预。

项目成果

Diaphragm plasticity following intrinsic laryngeal muscle denervation in rats.

大鼠内在喉肌去神经后膈肌的可塑性。

• DOI: 10.1097/00005768-200202000-00012
• 发表时间: 2002
• 期刊: Medicine and science in sports and exercise
• 影响因子: 4.1
• 作者: Rodman,JoshuaR;Gosselin,LucE;Horvath,PeterJ;Megirian,David;Farkas,GasparA
• 通讯作者: Farkas,GasparA

NMDA receptor-mediated modulation of ventilation in obese Zucker rats.

NMDA 受体介导的肥胖 Zucker 大鼠通气调节。

• DOI: 10.1038/sj.ijo.0801663
• 发表时间: 2001
• 期刊: International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity
• 作者: Lee,SD;Nakano,H;Farkas,GA
• 通讯作者: Farkas,GA

Opioidergic modulation of ventilatory response to sustained hypoxia in obese Zucker rats.

阿片能调节肥胖 Zucker 大鼠对持续缺氧的通气反应。

• DOI: 10.1038/oby.2001.53
• 发表时间: 2001
• 期刊: Obesity research
• 作者: Lee,SD;Magalang,UJ;Krasney,JA;Farkas,GA
• 通讯作者: Farkas,GA

GABAergic modulation of ventilation and peak oxygen consumption in obese Zucker rats.

GABAergic 对肥胖 Zucker 大鼠通气和峰值耗氧量的调节。

• DOI: 10.1152/jappl.2001.90.5.1707
• 发表时间: 2001
• 期刊: Journal of applied physiology (Bethesda, Md. : 1985)
• 作者: Lee,SD;Nakano,H;Farkas,GA
• 通讯作者: Farkas,GA

Role of nitric oxide in thermoregulation and hypoxic ventilatory response in obese Zucker rats.

• DOI: 10.1164/ajrccm.164.3.2010142
• 发表时间: 2001-08
• 期刊: American journal of respiratory and critical care medicine
• 影响因子: 24.7
• 作者: H. Nakano;Shin-Da Lee;ANDREW D. Ray-ANDREW D.-Ray-2239729907;J. Krasney;G. Farkas