The diurnal rhythm of forebrain of young and adenosine levels in the basal old rats
The diurnal rhythm of forebrain of young and adenosine levels in the basal old rats
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DOI：
10.1016/j.neuroscience.2003.09.015
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发表时间：
2004-01-01
期刊：
影响因子：
3.3
通讯作者：
Shiromani, PJ
中科院分区：
文献类型：
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作者：
Murillo-Rodriguez, E;Blanco-Centurion, C;Shiromani, PJ
随着年龄的增长，睡眠时间明显减少。这些症状包括睡眠碎片化、清醒时间增加、睡眠时间缩短、睡眠昼夜节律幅度减少、快速眼动睡眠减少以及脑电图δ波功率（0.3-4 Hz）大幅下降。老年大鼠在持续12小时的清醒状态下睡眠也会减少，这表明随着年龄的增长，睡眠驱动会减少。随着年龄增长导致睡眠减少的机制尚不清楚，但不能归因于与睡眠有关的神经元的丧失，因为年幼（3.5个月）和年老（21.5个月）大鼠的腹侧视前区（一个与产生睡眠有关的区域）的神经元数量相似。随着年龄的增长，睡眠驱动减少的一种可能性是，由于内源性睡眠因素的下降，睡眠-觉醒活跃的神经元受到的刺激可能减少了。在这里，我们通过关注嘌呤，腺苷（AD）来验证这一假设，这是一种在长时间睡眠后增加的睡眠因素。在实验1中，每隔1小时对基底前脑AD的微透析测量显示，在24小时的昼夜周期中，老年（21.5个月）大鼠与年轻大鼠相比，细胞外AD水平更高。在实验2中，老年大鼠保持清醒6小时（亮灯前半段）的AD累积量高于年轻大鼠。如果年老的老鼠有更多的阿尔茨海默病，那为什么它们睡得更少呢？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。我们得出的结论是，尽管老年大鼠有更多的阿尔茨海默病，但阿尔茨海默病受体对配体的敏感性降低，并没有像年轻大鼠那样以同样的强度转导阿尔茨海默病信号，这可能是老年人睡眠驱动下降的一个因素。(c) 2003年。Elsevier Ltd.出版。版权所有。
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. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved.