Hypoglycemia activates arousal-related neurons and increases wake time in adult rats.
Hypoglycemia activates arousal-related neurons and increases wake time in adult rats.
复制标题
低血糖会激活成年大鼠的觉醒相关神经元并增加觉醒时间。
DOI：
10.1016/j.physbeh.2007.03.003
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发表时间：
2007
影响因子：
2.9
通讯作者：
Morrison,AdrianR
中科院分区：
文献类型：
--
作者：
Tkacs,NancyC;Pan,Yanhua;Sawhney,Gagan;Mann,GraziellaL;Morrison,AdrianR
由于外源性或内源性胰岛素过量引起的低血糖症，会刺激中枢神经系统激活，导致激素分泌的反调节作用。在没有糖尿病的成年人中，睡眠期间发生的低血糖通常会在觉醒时产生皮质激活。然而，在患有1型糖尿病的成年人中，低血糖唤醒似乎迟钝或不存在。我们假设注射足以产生低血糖的胰岛素会诱导成年雄性大鼠觉醒。进行多导睡眠图研究以表征在增加睡眠的昼夜节律时间期间胰岛素注射对睡眠和清醒测量的影响。与基线日相比，胰岛素治疗使清醒时间增加了一倍多，从注射生理盐水后的18.4 ± 2.6%增加到胰岛素后的48.0 ± 5.5%。胰岛素注射也使快速眼动睡眠（REMS）从27.3 ± 1.8%降低至5.6 ± 1.3%。非快速眼动睡眠（NREMS）睡眠的时间百分比在盐水和胰岛素天之间没有差异，但是，胰岛素后的NREMS是碎片化的，发作次数增加，持续时间缩短。这些电生理学数据表明，胰岛素诱导的低血糖症是一个唤醒刺激大鼠，在非糖尿病成人。我们还研究了胰岛素对激活选定的唤醒相关神经元的免疫组化检测Fos的影响。胰岛素刺激后，食欲素（OX）神经元Fos免疫反应阳性率从注射生理盐水后的8.7 ± 4.9%增加到37 ± 9%。基底前脑胆碱能核也表现出胰岛素后Fos免疫反应性增加。这些相关的行为学和组织学数据为未来低血糖唤醒神经通路的研究提供了目标。
Hypoglycemia resulting from excess of exogenous or endogenous insulin elicits central nervous system activation that contributes to counterregulatory hormone secretion. In adult humans without diabetes, hypoglycemia occurring during sleep usually produces cortical activation with awakening. However, in adult humans with type 1 diabetes, hypoglycemic arousal appears blunted or absent. We hypothesized that insulin injection sufficient to produce hypoglycemia would induce awakening in adult male rats. Polysomnographic studies were carried out to characterize the effect of insulin injection on measures of sleep and waking during a circadian time of increased sleep. Compared to a baseline day, insulin treatment more than doubled the time spent awake, from 18.4±2.6% after saline injection to 48.0±5.5% after insulin. Insulin injection also reduced rapid eye movement sleep (REMS) from 27.3±1.8% to 5.6±1.3%. The percent of time in non-REM sleep (NREMS) sleep was not different between saline and insulin days, however, NREMS after insulin was fragmented, with increased number and decreased duration of episodes. These electrophysiological data indicate that insulin-induced hypoglycemia is an arousing stimulus in rats, as in nondiabetic adult humans. We also studied the effect of insulin on activation of selected arousal-related neurons using immunohistochemical detection of Fos. Fos-immunoreactivity increased in orexin (OX) neurons after insulin, from 8.7±4.9% after saline injection to 37±9% after insulin. Basal forebrain cholinergic nuclei also showed increased Fos-immunoreactivity after insulin. These correlated behavioral and histological data provide targets for future studies of the neural pathways underlying hypoglycemic arousal.