Murillo-Rodriguez E, Blanco-Centurion C, Gerashchenko D, Salin-Pascual R J, Shiromani P J
Department of Neurology, West Roxbury VA Medical Center and Harvard Medical School, Building 3, Room 2C109, 1400 VFW Parkway, West Roxbury, MA 02132, USA.
Neuroscience. 2004;123(2):361-70. doi: 10.1016/j.neuroscience.2003.09.015.
There are significant decrements in sleep with age. These include fragmentation of sleep, increased wake time, decrease in the length of sleep bouts, decrease in the amplitude of the diurnal rhythm of sleep, decrease in rapid eye movement sleep and a profound decrease in electroencephalogram Delta power (0.3-4 Hz). Old rats also have less sleep in response to 12 h-prolonged wakefulness (W) indicating a reduction in sleep drive with age. The mechanism contributing to the decline in sleep with aging is not known but cannot be attributed to loss of neurons implicated in sleep since the numbers of neurons in the ventral lateral preoptic area, a region implicated in generating sleep, is similar between young (3.5 months) and old (21.5 months) rats. One possibility for the reduced sleep drive with age is that sleep-wake active neurons may be stimulated less as a result of a decline in endogenous sleep factors. Here, we test this hypothesis by focusing on the purine, adenosine (AD), one such sleep factor that increases after prolonged W. In experiment 1, microdialysis measurements of AD in the basal forebrain at 1 h intervals reveal that old (21.5 months) rats have more extracellular levels of AD compared with young rats across the 24 h diurnal cycle. In experiment 2, old rats kept awake for 6 h (first half of lights-on period) accumulated more AD compared with young rats. If old rats have more AD then why do they sleep less? To investigate whether changes in sensitivity of the AD receptor contribute to the decline in sleep, experiments 3 and 4 determined that for the same concentration of AD or the AD receptor 1 agonist, cyclohexyladenosine, old rats have less sleep compared with young rats. We conclude that even though old rats have more AD, a reduction in the sensitivity of the AD receptor to the ligand does not transduce the AD signal at the same strength as in young rats and may be a contributing factor to the decline in sleep drive in the elderly.
随着年龄增长，睡眠会出现显著减少。这些变化包括睡眠碎片化、清醒时间增加、睡眠时段长度缩短、睡眠昼夜节律幅度减小、快速眼动睡眠减少以及脑电图δ波功率（0.3 - 4赫兹）大幅下降。老年大鼠在经历12小时长时间清醒后睡眠也较少，这表明随着年龄增长睡眠驱动力下降。导致睡眠随衰老而减少的机制尚不清楚，但并非归因于与睡眠相关的神经元损失，因为在腹外侧视前区（一个与产生睡眠有关的区域），年轻（3.5个月）和老年（21.5个月）大鼠的神经元数量相似。随着年龄增长睡眠驱动力降低的一种可能性是，由于内源性睡眠因子减少，睡眠 - 清醒活跃神经元受到的刺激可能减少。在此，我们通过关注嘌呤腺苷（AD）来检验这一假设，AD是一种在长时间清醒后会增加的睡眠因子。在实验1中，每隔1小时对基底前脑进行微透析测量AD，结果显示在24小时昼夜周期中，老年（21.5个月）大鼠的细胞外AD水平比年轻大鼠更高。在实验2中，与年轻大鼠相比，在开灯期的前半段保持清醒6小时的老年大鼠积累了更多的AD。如果老年大鼠有更多的AD，那么为什么它们睡眠更少呢？为了研究AD受体敏感性的变化是否导致睡眠减少，实验3和实验4确定，对于相同浓度的AD或AD受体1激动剂环己基腺苷，老年大鼠比年轻大鼠睡眠更少。我们得出结论，尽管老年大鼠有更多的AD，但AD受体对配体的敏感性降低，无法像年轻大鼠那样以相同强度传导AD信号
