SEROTONIN, AGING AND PLASTICITY--SLEEP BREATHING

睡眠呼吸障碍影响了2%-5%的成年人， 据估计，25%的65岁以上的人 经历一些睡眠呼吸暂停。这项提案将探讨与年龄有关的问题 与睡眠障碍有关的神经递质系统的变化 呼吸。我们建议确定5-羟色胺是否是潜在的 与年龄相关的上呼吸道控制变化的介体 对睡眠中的呼吸有负面影响。5-羟色胺能神经元的变化 输入可能会使老年人容易患上呼吸障碍综合征 包括阻塞性睡眠呼吸暂停(OSA)。我们的工作假设是 5-羟色胺能调制上呼吸道运动神经元 年龄越来越大。初步结果表明，这一数字有所下降 在老年动物舌下运动神经元的5-羟色胺能神经支配中， 我们建议通过进一步阐明5-羟色胺能系统的变化 研究5-羟色胺终末密度随年龄的变化， 特异性5-羟色胺受体和选择性5-羟色胺转运体 在选择性支配上呼吸道肌肉的脑干核团中。 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与年龄相关的 这些核团的5-羟色胺能输入的变化不同于 雄性和雌性。该项目的第三个目标是确定 5-羟色胺能传入上呼吸道控制系统是否可以 通过行为干预在老年动物身上得到增强。初步 结果表明，慢性间歇性低氧会产生一种 5-羟色胺依赖的呼吸活动增强 幼年大鼠舌下神经运动核和5-羟色胺能神经元的增加 神经支配。从这些研究中获得的信息将会增加 我们对年龄相关潜在机制的理解 睡眠障碍，并开辟了一个研究领域，有望 导致成功的治疗干预。

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.