ADENOSINE AND SLEEP REGULATION IN AGING RATS

衰老大鼠的腺苷和睡眠调节

• 批准号: 6299316
• 负责人: Priyattam J. Shiromani
• 金额: $ 19.85万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6299316
• 关键词: REM sleep; adenosine; age difference; aging; animal old age; circadian rhythms; electroencephalography; galanin; gene expression; histology; homeostasis; immunocytochemistry; in situ hybridization; juvenile animal; laboratory rat; messenger RNA; neuroanatomy; neuroregulation; neurotransmitters; preoptic areas; protooncogene; purinergic receptor; receptor expression; sleep; sleep regulatory center; wakefulness

A pronounced decline in sleep occurs with aging. This deficit in sleep with aging presents a major problem for elderly individuals, causing daytime sleepiness and impairing alertness. However, the mechanism for this change in the sleep cycle with aging is not understood. In the previous cycle of this Program Project Grant, the hypothesis was explored that the deficit in sleep in aged individuals was due to a deterioration in the circadian pacemaker, i.e, suprachiasmatic nucleus (SCN). However, results from Czeisler's group indicate that older subjects show no change in period of the temperature rhythm. These findings raise the possibility that there is no change in the SCN's pacemaking ability, but that other coupling pathways might decline with age. One possibility is that homeostatic elements regulating sleep- wakefulness might be impaired with aging. Our studies will directly address the hypothesis that the defect in sleep caused by aging is a lack of responsiveness in the ventrolateral preoptic nucleus (VLPO) neurons to the accumulation of adenosine. Specific aim 1 will test the integrity of the VLPO neurons in young and old rats. We predict that in older animals for a given amount of prior wakefulness there is less c-fos expression in VLPO. This would indicate levels in VLPO neuron. We predict that for a given amount for prior wakefulness older rats will have less galanin mRNA levels in VLPO compared to young rats. Specific aim 2 will test the hypothesis that there may be reduced responsiveness of VLPO neurons to accumulation of adenosine because of a reduction in expression of adenosine receptors by VLPO neurons or their afferents during aging. Specific aim 3 will test the hypothesis that preoptic neurons themselves are hyporesponsive to adenosine in aged animals.

随着年龄的增长，睡眠明显减少。随着年龄的增长，睡眠不足是老年人的一个主要问题，导致白天嗜睡和警觉性受损。然而，这种睡眠周期随年龄增长而变化的机制尚不清楚。在本计划项目资助的上一个周期中，探讨了老年人睡眠不足是由于昼夜节律起搏器（即视交叉上核（SCN））恶化的假设。然而，来自Czeisler小组的结果表明，老年受试者的温度节律周期没有变化。这些发现提出了一种可能性，即SCN的起搏能力没有变化，但其他耦合途径可能会随着年龄的增长而下降。一种可能性是，调节睡眠-觉醒的自我平衡因素可能会随着年龄的增长而受损.我们的研究将直接解决这一假设，即衰老引起的睡眠缺陷是腹外侧视前核（VLPO）神经元对腺苷积累缺乏反应。具体目标1将测试年轻和老年大鼠中VLPO神经元的完整性。我们预测，在老年动物为一定量的先前觉醒有较少的c-fos表达VLPO。这将指示VLPO神经元中的水平。我们预测，对于一定量的先前觉醒，老年大鼠的VLPO中甘丙肽mRNA水平低于年轻大鼠。具体目标2将检验以下假设：由于衰老期间VLPO神经元或其传入神经的腺苷受体表达减少，VLPO神经元对腺苷蓄积的反应性可能降低。具体目标3将检验老年动物视前神经元本身对腺苷反应迟钝的假设。