Neurophysiology Division, Department of Physiology, Defence Institute of Physiology & Allied Sciences, Defence Research and Development Organization, Timarpur, Delhi, India.
Neurochem Int. 2011 Jan;58(1):112-8. doi: 10.1016/j.neuint.2010.11.003. Epub 2010 Nov 12.
Sojourners to high altitude experience poor-quality of sleep due to hypobaric hypoxia (HH). Brain neurotransmitters are the key regulators of sleep wakefulness. Scientific literature has limited information on the role of brain neurotransmitters involved in sleep disturbance in HH. The present study aimed to investigate the time dependent changes in neurotransmitter levels and enzymes involved in the biosynthesis of brain neurotransmitters in frontal cortex, brain stem, cerebellum, pons and medulla and the effect of these alterations on sleep architecture in HH. Thirty adult Sprague-Dawley rats, body weight of 230-250 g were exposed to simulated altitude ∼7620 m, 282 mm Hg, partial pressure of O(2) 59 mm Hg for 7 and 14 days continuously in an animal decompression chamber. After 7 and 14 days of HH, brain nor-epinephrine and dopamine levels were significantly increased in frontal cortex, brain stem, cerebellum and pons and medulla whereas serotonin level was significantly reduced in frontal cortex and pons and medulla after 14 days of HH. Tyrosine hydroxylase level in locus coeruleus (LC) was significantly increased whereas Choline Acetyl Transferase and Glutamic Acid Decarboxylase (GAD) levels were significantly reduced in laterodorsal-tegmentum and pedunculopontine-tegmentum after 7 days of HH. GAD was also reduced in LC after 7 days HH. Alteration in these neurotransmitters and enzyme levels was accompanied with reduction in quality and quantity of sleep. There was a significant increase in sleep latency, rapid eye movement (REM) latency, duration of active awake, quiet awake, quiet sleep and a significant decrease in duration of REM sleep and deep sleep on day 7 and 14 of HH. It was concluded that HH alters the expression of enzymes linked to sleep neurotransmitter synthesis pathway and subsequent loss of homeostasis at neurotransmitter level disrupts the sleep pattern in hypobaric hypoxia.
移居到高海拔地区的人会因低气压缺氧（HH）而睡眠质量差。脑神经递质是调节睡眠觉醒的关键。科学文献中关于 HH 中涉及睡眠障碍的脑神经递质的信息有限。本研究旨在研究神经递质水平及参与脑神经递质生物合成的酶在额叶皮质、脑干、小脑、脑桥和延髓中的时间依赖性变化，以及这些变化对 HH 中睡眠结构的影响。30 只成年 Sprague-Dawley 大鼠，体重 230-250 克，连续 7 和 14 天在动物减压室中暴露于模拟海拔 7620 米，282 毫米汞柱，氧气分压 59 毫米汞柱。HH 后 7 和 14 天，额叶皮质、脑干、小脑和脑桥延髓中的脑去甲肾上腺素和多巴胺水平显著升高，而 14 天后额叶皮质和脑桥延髓中的 5-羟色胺水平显著降低。蓝斑（LC）中的酪氨酸羟化酶水平显著升高，而 7 天后外侧隔核和脚桥被盖核中的胆碱乙酰转移酶和谷氨酸脱羧酶（GAD）水平显著降低。7 天后 LC 中的 GAD 也减少。这些神经递质和酶水平的改变伴随着睡眠质量和数量的减少。睡眠潜伏期、快速眼动（REM）潜伏期、活跃清醒、安静清醒、安静睡眠的持续时间显著增加，REM 睡眠和深睡眠的持续时间显著减少，在 HH 第 7 和 14 天。研究结论为，HH 改变了与睡眠神经递质合成途径相关的酶的表达，随后神经递质水平失去内稳态，破坏了低气压缺氧中的睡眠模式。
