SEROTONIN, AGING AND PLASTICITY--SLEEP BREATHING

血清素、衰老和可塑性——睡眠呼吸

• 批准号: 2706049
• 负责人: MARY BEHAN
• 金额: $ 7.2万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2706049
• 关键词: aging; axon; female; gender difference; hypoglossal nucleus; hypoxia; immunocytochemistry; innervation; laboratory rat; male; neural plasticity; respiratory airflow disorder; serotonin; serotonin receptor; serotonin transporter; sleep apnea; sleep disorders

Sleep disordered breathing affects 2-5 percent of the adult population, and it is estimated that 25 percent of people over the age of 65 experience some sleep apnea. This proposal will explore age-related changes in a neurotransmitter system involved in sleep disordered breathing. We propose to determine whether serotonin is a potential mediator of the age-associated changes in upper airway control that negatively impact on breathing during sleep. Changes in serotonergic input may predispose aging individuals to disordered breathing syndromes including obstructive sleep apnea (OSA). Our working hypothesis is that serotonergic modulation of upper airway motoneurons decreases with increasing age. Preliminary results suggest that there is a decrease in serotonergic innervation of hypoglossal motoneurons in older animals, We propose to further elucidate changes in the serotonergic system by investigating age-associated changes in serotonin terminal density, specific serotonin receptors, and the selective serotonin transporter in brainstem nuclei that selectively innervate upper airway musculature. As obstructive sleep apnea occurs with greater frequency in males, a second goal of this project is to determine whether age-associated changes in the serotonergic input to these nuclei are dissimilar in males and females. A third goal of this project is to determine whether serotonergic input to the upper airway control system can be enhanced in old animals by a behavioral intervention. Preliminary results indicate that chronic, intermittent hypoxia produces a serotonin-dependent enhancement of respiratory activity in the hypoglossal motor nucleus of young rats, and an increase in serotonergic innervation. The information derived from these studies will increase our understanding of the potential mechanisms underlying age-associated sleep disorders, and open up an area of research that will hopefully lead to successful therapeutic intervention.

睡眠呼吸障碍影响2- 5%的成年人， 据估计，65岁以上的人中， 睡眠呼吸暂停 该提案将探讨与年龄有关的 神经递质系统的变化与睡眠障碍有关 呼吸了 我们建议确定血清素是否是一种潜在的 上呼吸道控制中年龄相关变化的调节剂， 对睡眠时的呼吸有负面影响。 肾上腺素能的变化 输入可能使老年人易患呼吸紊乱综合征 包括阻塞性睡眠呼吸暂停（OSA）。 我们的假设是 上呼吸道运动神经元的突触能调节随着 年龄增长。 初步结果显示， 在老年动物舌下神经运动神经元的突触能神经支配中， 我们建议通过以下方法进一步阐明β-肾上腺素能系统的变化： 研究与年龄相关的5-羟色胺末端密度变化， 特异性血清素受体和选择性血清素转运体 在选择性支配上呼吸道肌肉组织的脑干核团中。 由于阻塞性睡眠呼吸暂停在男性中发生的频率更高， 该项目的第二个目标是确定是否与年龄相关 在这些核中的电子能输入的变化是不同的， 雄性和雌性。 本项目的第三个目标是确定 上呼吸道控制系统的肾上腺素能输入是否可以 通过行为干预在老年动物中得到增强。初步 结果表明，慢性，间歇性缺氧产生 呼吸活动的依赖性增强 年轻大鼠舌下神经运动核，并增加 神经支配 从这些研究中获得的信息将增加 我们对年龄相关的潜在机制的理解 睡眠障碍，并开辟了一个研究领域， 导致成功治疗干预。