快速眼动睡眠剥夺大鼠中缝背核内galanin阳性神经元表达及抑郁行为的研究

目的:研究不同时间快速眼动睡眠剥夺大鼠中缝背核内galanin阳性神经元的表达,抑郁行为的变化以及两者间的相互关系。方法:SD大鼠,雄性,采用完全随机对照分组:正常对照组,24h快速眼动睡眠剥夺组,48h快速眼动睡眠剥夺组,72h快速眼动睡眠剥夺组。用小平台水环境法建立快速眼动睡眠剥夺大鼠模型,正常对照组大鼠常规饲养。分别对各组大鼠进行强迫游泳实验,悬尾实验,记录抑郁行为得分;然后对各组大鼠脑片进行免疫荧光组化染色,检测中缝背核内galanin阳性神经元的表达。结果:各快速眼动睡眠剥夺组大鼠抑郁行为的得分较正常对照组均增高,尤以72h快速眼动睡眠剥夺组的得分较高,同时,各快速眼动睡眠剥夺组大鼠中缝背核内galanin阳性神经元的数量较正常对照组均增多,尤其以72h快速眼动睡眠剥夺组阳性神经元的表达增多显著。结论:galanin参与快速眼动睡眠剥夺发生后的生物学效应,中缝背核内galanin阳性神经元的表达上调可能与快速眼动睡眠剥夺大鼠抑郁行为的变化有关。     

颈交感干离断缓解快速眼动睡眠剥夺大鼠学习记忆障碍

目的:观察颈交感干离断(TCST)对快速眼动睡眠剥夺(RSD)大鼠空间学习记忆的作用及其潜在机理。方法:32只成年雄性SD大鼠分成假手术组(sham)、RSD组、TCST组和TCST干预的RSD组(RSD+TCST组)。采取改良的多站台水环境法建立大鼠RSD模型。选取Morris水迷宫实验检测各组大鼠空间学习记忆能力,Western Blot检测caspase-3蛋白表达,通过ELISA评估海马组织去甲肾上腺素(NE)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)和白细胞介素1β(IL-1β)的水平。结果:TCST明显提高了RSD大鼠的空间学习记忆能力(P <0.05),TCST显著抑制RSD大鼠海马组织NE的释放(P <0.05)、炎症反应(P <0.05)与凋亡(P <0.05)。结论:TCST可通过抑制交感神经活动,缓解海马组织炎症与减少细胞凋亡来改善RSD大鼠空间学习记忆障碍。     

右美托咪定对快速眼动睡眠剥夺大鼠学习记忆障碍的影响

目的:探讨右美托咪定对快速眼动(REM)睡眠剥夺大鼠学习记忆障碍的影响。方法:将64只健康雄性SD大鼠随机分为对照组(control)、快速眼动睡眠剥夺组(RSD)、右美托咪定组(DEX)和右美托咪定干预的快速眼动睡眠剥夺组(RSD+DEX)。每组16只。应用改良多平台水环境法建立大鼠快速眼动睡眠剥夺模型,通过腹腔内注射给予大鼠右美托咪定,采用Morris水迷宫检测大鼠空间学习记忆能力,采用尼氏染色法检测大鼠海马神经元形态学改变,同时应用试剂盒检测大鼠海马组织匀浆中丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性。结果:与RSD组大鼠相比,RSD+DEX组大鼠逃避成功潜伏期趋于缩短(P 0. 05),穿越平台次数与目标象限时间百分比均明显增加(均P 0. 05),MDA含量减少,SOD活性均增加(P 0. 05),海马CA1区神经元排列较规则,尼氏小体明显增加。结论:右美托咪定能够改善REM睡眠剥夺大鼠学习记忆损伤,这可能与右美托咪定缓解REM睡眠剥夺大鼠海马神经细胞氧化应激和恢复受损细胞有关。     

抑制一氧化氮合成酶对大鼠睡眠及5—羟色胺神经元免疫反应的影响

采用多导描记及免疫组化方法，观察了侧脑室和腹腔给予硝基左旋精氨酸对慢性植入电采大鼠睡眠量及中缝背核５－羟色胺神经元免疫阳性反应的影响，结果表明：Ｌ－ＮＮＡ显著抑制慢波睡眠的快眼动睡眠，与对照相比较，觉醒时间延长。     

5-羟色胺3A受体在成年小鼠海马中间神经元中的分布

目的:利用成年5-HT3AR-BACEGFP转基因小鼠,研究5-羟色胺3A受体(5-HT3AR)在海马中间神经元中的分布情况。方法:成年5-HT3AR-BACEGFP转基因小鼠经心脏灌注固定后,利用免疫荧光双标记方法,并结合激光共焦显微镜扫描技术,观察5-HT3AR在成年5-HT3AR-BACEGFP转基因小鼠海马中不同中间神经元内的表达和分布情况。结果:5-HT3AR在成年小鼠整个海马中都有分布,且主要在CA1区、CA2/CA3区和齿状回有大量5-HT3AR免疫阳性细胞;激光共聚焦显微镜下观察到5-HT3AR阳性产物在细胞核、细胞浆和树突上均有表达;免疫荧光双标实验结果表明5-HT3AR阳性产物在CB(calbindin),CR(calretinin),Reelin,Som(somatostatin),NPY(neuropeptide Y)和VIP(vasoactive intestinal peptide)免疫阳性神经元中表达,但在PV(parvalbumin)免疫阳性神经元中不表达。定量结果显示:几乎所有的VIP阳性神经元均表达5-HT3AR阳性,约3/4的CR阳性神经元表达5-HT3AR,约1/2的CB、Reelin、NPY和Som阳性神经元表达5-HT3AR阳性;约1/4的5-HT3AR阳性神经元中表达Reelin,1/5的表达Som,5-HT3AR/CB和5-HT3AR/CR双标神经元各占5-HT3AR阳性神经元的1/10左右。结论:5-HT3AR-BACEGFP转基因小鼠能够作为研究海马中5-HT3AR功能及其在中间神经元中的作用机制研究的工具鼠。     

mGluR5参与小鼠睡眠剥夺快速抗抑郁作用的机制研究

目的:探讨代谢型谷氨酸受体5(mGluR5)在睡眠剥夺抗抑郁作用中的机制。方法:采用坐骨神经分支选择损伤(SNI)方法制备神经病理性痛小鼠伴发负性情绪的动物模型,利用旷场和高架十字实验评估小鼠的焦虑样行为,利用悬尾实验和糖水偏好实验评估小鼠的抑郁样行为,利用von-Frey方法检测小鼠的机械痛敏行为;采用温和处理的方法对有抑郁样行为小鼠进行睡眠剥夺,并评估睡眠剥夺对小鼠焦虑、抑郁样行为的影响;采用Western Blot方法检测SNI模型及睡眠剥夺后小鼠内侧前额叶皮层(mPFC)内mGluR5表达量的变化;进一步对小清蛋白(PV)阳性神经元mGluR5敲除的小鼠进行睡眠剥夺前后的行为学检测。结果:SNI模型小鼠40 d后出现焦虑样行为,60 d左右出现抑郁样行为,睡眠剥夺可明显缓解其抑郁样行为,但是对焦虑样行为和机械痛敏无影响;抑郁情绪及睡眠剥夺对mPFC内mGluR5表达水平无影响,但PV~+神经元mGluR5敲除的小鼠表现出抑郁样行为,且睡眠剥夺对其抑郁样行为无缓解作用。结论:睡眠剥夺可以明显缓解神经病理性痛伴发的抑郁样行为,PV~+神经元的mGluR5在抑郁样行为的发生和睡眠剥夺的抗抑郁效果中可能发挥着重要的作用。     

抑制一氧化氮合成酶对大鼠睡眠及5－羟色胺神经元免疫反应的影响

采用多导描记及免疫组化方法，观察了侧脑室和腹腔给予硝基左旋精氨酸（Ｌ－ＮＮＡ）对慢性植入电极大鼠睡眠量及中缝背核５－羟色胺（５－ＨＴ）神经元免疫阳性反应的影响。结果表明：Ｌ－ＮＮＡ显著抑制慢波睡眠和快眼动睡眠，与对照相比较，觉醒时间延长。脑室给予Ｌ－ＮＮＡ使中缝背核５－ＨＴ神经元阳性细胞增多。提示一氧化氮合成抑制所致的睡眠抑制可能与中缝背核５－ＨＴ神经元免疫阳性反应增强有关。     

特发性和继发性快速眼动睡眠行为障碍的睡眠结构研究

目的：探讨快速眼动睡眠行为障碍（REM sleep behavior disorder,RBD）患者的睡眠结构改变。方法：纳入的22例患者符合国际睡眠障碍协会（第2版）的RBD诊断标准,16例患者符合RBD主要诊断标准以及英国脑库的PD、2005年国际路易体痴呆协作组或者2008年多系统萎缩第2版的诊断标准。同时纳入年龄、性别匹配的健康对照19例。利用日本光电32信道9200K脑电图机,所有患者均完成多项睡眠图监测（PSG）,记录脑电图、眼球运动、下颌和肢体肌电活动、心电图、经鼻气流、胸腹部呼吸运动、血氧、鼾声等多个项目,并录像监测患者的行为。使用Polysmith软件和视觉评估分析睡眠结构、呼吸、运动等相关指标。结果：RBD患者展现了典型临床表现和电生理改变。特发性RBD组（72．7％）较继发性RBD组（43．8％）显示有更多的夜间活动和言语,差异有统计学意义（P=0．071）。特发性RBD在睡眠结构并未发生明显改变,仅有周期性腿动（PLM）指数增高。继发性RBD与特发性RBD和健康对照相比,总体睡眠时间缩短、睡眠效率减低、睡眠潜伏期和REM潜伏期延迟、Ⅱ期和REM睡眠减少、Ⅰ期睡眠增加、低通气指数增高、PLM指数增高。结论：特发性RBD患者具有更多的夜间行为异常,而睡眠结构无改变,仅有PLM指数增加;而继发性RBD出现明显的睡眠结构紊乱、呼吸紊乱以及PLM异常。     

脑梗死患者记忆减退与快速眼动睡眠的关系

目的：探讨脑梗死患者记忆减退与快速眼动（ＲＥＭ）睡眠的关系。方法：对４０例脑梗死患者进行记忆测定和多导睡眠图通宵描记,分析有关睡眠参数并与２２名正常人比较。结果：脑梗死患者睡眠潜伏期长,醒转次数增多,总睡眠时间减少,睡眠效率低,ＲＥＭ时间减少,ＲＥＭ活动度和密度均降低（Ｐ＜００１）,其记忆减退与ＲＥＭ减少具有相关性（ｒ＝０６８,Ｐ＜００１）。结论：脑梗死患者不但有睡眠量的减少而且有睡眠质的改变,尤其ＲＥＭ睡眠减少与记忆减退有密切关系。     

Abnormal response of melanin-concentrating hormone deficient mice to fasting: hyperactivity and rapid eye movement sleep suppression

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that has been implicated in energy homeostasis. Pharmacological studies with MCH and its receptor antagonists have suggested additional behavioral roles for the neuropeptide in the control of mood and vigilance states. These suggestions have been supported by a report of modified sleep in the MCH-1 receptor knockout mouse. Here we found that MCH knockout (MCH(-)(/)(-)) mice slept less during both the light and dark phases under baseline conditions. In response to fasting, MCH(-)(/)(-) mice exhibited marked hyperactivity, accelerated weight loss and an exaggerated decrease in rapid eye movement (REM) sleep. Following a 6-h period of sleep deprivation, however, the sleep rebound in MCH(-)(/)(-) mice was normal. Thus MCH(-)(/)(-) mice adapt poorly to fasting, and their loss of bodyweight under this condition is associated with behavioral hyperactivity and abnormal expression of REM sleep. These results support a role for MCH in vigilance state regulation in response to changes in energy homeostasis and may relate to a recent report of initial clinical trials with a novel MCH-1 receptor antagonist. When combined with caloric restriction, the treatment of healthy, obese subjects with this compound resulted in some subjects experiencing vivid dreams and sleep disturbances.     

Effect of rapid eye movement sleep deprivation on rat brain Na-K ATPase activity

Since rapid eye movement (REM) sleep deprivation has been reported to affect the neuronal excitability in the brain, it was hypothesized that a change in the neuronal membrane-bound Na-K ATPase activity might be at least one of the factors inducing such a change. Therefore, in this study rats were deprived of REM sleep by using the platform technique and enzyme activity was estimated in the whole brain, in different regions of the brain and in microsomal preparations. Deprivation was carried out for varying periods and suitable control experiments were conducted to rule out the possibility of nonspecific effects. The observation supported our hypothesis and showed primarily that the deprivation increased the enzyme activity in the rat brain. It showed also that the pons and the medulla were the first sites to be affected by deprivation. The probable mechanism producing such a change is discussed.     

Disruptive effects of rapid eye movement sleep deprivation on long-term memory

The fact that sleep is associated with very active endogenous neural (chemical and electrical) processes, suggests that these processes may be involved in the maintenance of long-term memory storage. The present experiments were designed to examine the hypothesis that rapid eye movement (REM) sleep deprivation will produce impairment of long-term memory. Mice deprived of REM sleep for 3, 5 or 7 continuous days, during the interval between a one-trial inhibitory avoidance training experience and a subsequent retention test, displayed a temporary retrograde amnesia when tested 30 min or three hr following termination of REM deprivation. The mice did not recover from the amnesia if electroconvulsive shock was administered immediately following the interval of REM sleep deprivation. In a further study, the generality of these findings was obtained by depriving mice of REM sleep during the interval between a discrimination training experiment in a black-white T-maze and the subsequent retention test.     

不同时长REM期睡眠剥夺及莫达非尼干预后大鼠下丘脑Orexin A神经元的表达

目的:探讨不同程度快动眼睡眠(REM)期睡眠剥夺(sleep deprivation,SD)及莫达非尼干预后大鼠下丘脑Orexin A神经元的表达。方法:将成年雄性Sprague-Dawley大鼠随机分为和SD组和对照组,SD组又分为用药组(drug group,DG)和非用药组(non-drug group,NDG),每组分SD12,24,48,72,96h共5个小组;对照组(cage control,CC)1个小组,正常饲养于笼中。每小组3只大鼠。采用小平台水环境法建立大鼠REM期SD模型。免疫组化方法观察大鼠下丘脑Orexin A阳性神经元的数量。结果:Orexin A阳性表达在SD12,24h时长的DG组与NDG组表达较CC组均有增加(P0.05)而二者之间差别不明显(P0.05);在SD48,72,96h时长的NDG组的表达较CC组下降(P0.05),而DG组和CC组间无显著差异(P0.05)且明显高于NDG组表达(P0.05)。结论:推测莫达非尼可能是通过活化下丘脑促觉醒肽Orexin A的分泌和表达实现促觉醒作用。     

The effects of rapid eye movement sleep deprivation during late pregnancy on newborns' sleep

Sleep deprivation during pregnancy is an emerging concern, as it can adversely affect the development of the offspring brain. This study was conducted to evaluate the effects of deprivation of rapid eye movement (REM) sleep during the third term of pregnancy on the sleep–wake profiles of neonates in the Wistar rat model. Sleep–wake patterns were assessed through electrophysiological measures and behavioural observations during postnatal days 1–21 on pups born to REM sleep‐deprived dams and control rats. Pups of REM sleep‐deprived dams had active sleep that was not only markedly higher in percentage during all the days studied, but also had reduced latency during later postnatal days 15–21. Quiet sleep and wake periods were lower. These factors, along with less frequent but longer sleep–wake cycles, indicated maturational delay in the sleep–wake neural networks. The disruption of time‐bound growth of sleep–wake neural networks was substantiated further by the decreased slope of survival plots in the sleep bouts. Examination of altered sleep–wake patterns during early development may provide crucial information concerning deranged neural development in the offspring. This is the first report, to our knowledge, to show that maternal sleep deprivation during pregnancy can delay and impair the development of sleep–wake profile in the offspring.     

Daily rhythm of locomotor activity is abolished during rapid eye movement sleep deprivation in the rat

Applying a modified flowerpot technique, which made it possible to use a test animal as its own control, twenty-four hour cycles of locomotor activity were recorded in eight juvenile male rats on 12/12 hr light/dark (LD) schedule during six days of rapid eye movement (REM) sleep deprivation. It was found that the LD difference in locomotor activity unrelated to feeding was instantaneously abolished during REM sleep deprivation. The daily rhythm of food-directed activity, however, was only gradually attenuated. Due to this equalisation in the light and dark activity the rats gave an impression of hyperactivity during the light hours although the total daily motor output after an initial increase returned close to the baseline value.     

Effect of rapid eye movement sleep deprivation on allergen-induced airway responses in a rat model of asthma

BACKGROUND: Nocturnal airway narrowing is a common characteristic of asthma that remains poorly understood. Sleep itself or rapid eye movement (REM) sleep has been suspected to play a role in the etiology of nocturnal asthma; however, only inconsistent findings have so far been produced. The purpose of this study was to examine the effect of sleep deprivation, particularly REM sleep, using the classical platform (flowerpot) method on asthmatic responses in a rat model of asthma, in a situation of immobilization stress. METHODS: After the rats had been randomly divided into three groups of 9 including (1) a caged control group, (2) a large (sham) platform group, and (3) a small platform group, we investigated the effect of REM sleep deprivation over a 72-hour period on both the antigen-induced immediate asthmatic response (IAR) and late asthmatic response (LAR) including the changes of stress hormones. RESULTS: The small platform group showed significantly lower plasma histamine levels and higher plasma adrenaline levels during the IAR compared to the control group (p < 0.05). The number of eosinophils in either the bronchoalveolar lavage fluid or the bronchial lamina propria during the LAR in the small platform group was reliably suppressed compared to the other groups (p < 0.05). No significant differences were found in the plasma corticosterone and noradrenaline levels among the three groups, irrespective of the phase of the asthmatic response. CONCLUSIONS: Our results indicate that REM sleep contributes to nocturnal asthma, possibly due to an alteration of the sympathetic nervous function.     

Differential effects of waking from non-rapid eye movement versus rapid eye movement sleep on cardiovascular activity

The occurrence of cardiovascular events increases in the morning, and while the mechanism responsible is yet to be determined, possible contributors include surges in sympathetic activity and concurrent rises in blood pressure (BP). This study tested the hypothesis that the increase in sympathetic dominance and the surge in BP were greater when waking spontaneously from Stage 2 sleep compared with waking from rapid eye movement (REM) sleep. Twenty healthy young adults had overnight polysomnography, including electrocardiogram measurements. Spectral analysis of heart rate variability (HRV) was conducted on 2-min blocks of stable data selected from the last 30 min of sleep and during 30 min of resting wakefulness (supine) immediately following sleep. Outputs included absolute low frequency (LF) and high frequency (HF) power, the LF/HF ratio, heart rate (HR) and BP. To investigate the effect of waking from Stage 2 or REM sleep on HRV and BP responses, two-way analyses of variance ( anova s) (Stage 2 versus REM) with repeated measures (sleep versus morning wakefulness) were performed. It was found that waking from Stage 2 sleep was associated with significant increases in HR ( P  = 0·002) and BP ( P  < 0·001), as well as a tendency towards an increase in the LF/HF ratio ( P  = 0·08), whereas measurements during REM sleep and subsequent wakefulness were similar ( P  > 0·05). The greater increase in BP and HR when waking from Stage 2 sleep compared with REM sleep suggests that in vulnerable populations, waking from Stage 2 sleep could be an adjunct risk factor of cardiovascular events during the morning period.     

Sleep deprivation suppresses the increase of rapid eye movement density across sleep cycles

We investigated the association between rapid eye movement (REM) density (REMd) and electroencephalogram (EEG) activity during non‐rapid eye movement (NREM) and REM sleep, within the re‐assessment, in a large sample of normal subjects, of the reduction of oculomotor activity in REM sleep after total sleep deprivation (SD). Coherently with the hypothesis of a role of homeostatic sleep pressure in influencing REMd, a negative correlation between changes in REMd and slow‐wave activity (SWA) was expected. A further aim of the study was to evaluate if the decreased REMd after SD affects ultradian changes across sleep periods. Fifty normal subjects (29 male and 21 female; mean age = 24.3 ± 2.2 years) were studied for four consecutive days and nights. Sleep recordings were scheduled in the first (adaptation), second (baseline) and fourth night (recovery). After awakening from baseline sleep, a protocol of 40 h SD started at 10:00 hours. Polysomnographic measures, REMd and quantitative EEG activity during NREM and REM sleep of baseline and recovery nights were compared. We found a clear reduction of REMd in the recovery after SD, due to the lack of REMd changes across cycles. Oculomotor changes positively correlated with a decreased power in a specific range of fast sigma activity (14.75–15.25 Hz) in NREM, but not with SWA. REMd changes were also related to EEG power in the 12.75–13.00 Hz range in REM sleep. The present results confirm the oculomotor depression after SD, clarifying that it is explained by the lack of changes in REMd across sleep cycles. The depression of REMd can not simply be related to homeostatic mechanisms, as REMd changes were associated with EEG power changes in a specific range of spindle frequency activity, but not with SWA.