复方灵芝口服液对睡眠剥夺大鼠睡眠的影响

摘要：目的：探讨复方灵芝口服液对睡眠剥夺大鼠睡眠的影响。方法：利用腹腔注射氯苯丙氨酸（PCPA）制造睡眠剥夺模型,参照《保健食品检验与评价技术规范实施手册》（2003版）中的标准检测复方灵芝口服液是否具有改善睡眠的作用。结果：复方灵芝口服液可延长戊巴比妥钠诱导的睡眠时间（P＜0.05）,但对增加睡眠剥夺大鼠的入睡动物数和缩短巴比妥钠诱导的潜伏期无明显作用（P＞0.05）,且无直接睡眠作用。结论：复方灵芝口服液可明显延长戊巴比妥钠诱导的睡眠时间。     

睡眠剥夺对认知功能的影响研究进展

睡眠剥夺(sleep deprivation,SD)是一种由于环境或自身原因无法满足正常睡眠的情况.认知是个体认识和理解事物的心理过程,包括对自己与环境的确定、感知、注意、学习和记忆、思维和语言等.认知功能由多个认知域组成,包括记忆、计算、时空间定向、结构能力、执行能力、语言理解和表达及应用等方面.SD可对认知功能产生一定影响,如清醒度、警觉性及注意力下降;感官知觉能力下降;学习记忆能力下降等.SD可能增加氧自由基产生,改变神经递质动态分布,损伤海马结构,诱导异常基因表达以及抑制长时程增强效应,引起脑内神经结构状态紊乱,导致认知功能障碍.本文从SD所致认知障碍的表现形式,认知障碍的可能机制以及SD与神经变性的关系三个方面探讨SD对认知功能的影响.     

莫达非尼对睡眠剥夺条件下工作记忆的影响

目的:观察在睡眠剥夺条件下莫达非尼对工作记忆的改善作用,为此药在我军的应用策略提供实验依据。方法:18名健康男性志愿者,在两次睡眠剥夺实验中交叉服用莫达非尼和安慰剂,睡眠剥夺时间从第一天的07:00到第3d的07:00,并于第二天的0:00、12:00和第三天的0:00分别服用莫达非尼100mg或安慰剂。采用随机双盲设计给药,并在第一天的07:00、第二天的02:00和14:00以及第三天的02:00和07:00安排工作记忆测验。结果:工作记忆测验中,两组的反应时和正确率均有统计学差异(P<0.01),莫达非尼组的反应时要快于安慰剂组,正确率也要高于安慰剂组。莫达非尼对工作记忆的改善效果随着睡眠剥夺时间的延长而更趋明显。结论:莫达非尼对睡眠剥夺条件下个体的工作记忆有改善作用,是较为理想的睡眠剥夺对抗药物。     

从睡眠剥夺树qu（TBC）尿液提取内源性“睡眠因子”的研究

本研究报道从睡眠剥夺（ＳＤ）４８－７２ｈ的灵长类原宗Ｔｕｐａｉａ ｂｅｌａｎｇｅｒｉ ｃｈｉｎｅｎ－ｓｉｓ（ＴＢＣ）提取内源性“睡眠因子”Ｓ２Ｃ和Ｓ４Ｂ。收集的尿液经超滤,清液冻干经Ｓｅｐｈａｄｅｘ Ｇ１５分离内源性“睡眠因子”Ｓ２Ｃ和Ｓ４Ｂ。收集的尿液经滤,清液冻干经ＳｅｐｈａｄｅｘＧ１５分离得到Ｆｒａｃｔｉｏｎ Ｉ－Ｖ。活性测定发现Ｆｒａｃｔｉｏｎ－Ⅲ（Ｓ２Ｃ）呈现显著δ－增强促眠效应。经Ｓｅ     

睡眠剥夺对大鼠咬肌超微结构的影响

目的:应用电镜观察睡眠剥夺对大鼠咬肌超微结构的影响.方法:35只Wistar大鼠,随机分为5组:睡眠剥夺1d组、5d组、9d组、正常对照组和大平台对照组.采用改良多平台睡眠剥夺法(modified multiple plat-form method,MMPM)建立大鼠SD模型,观察咬肌超微结构的变化.结果:睡眠剥夺5d组大鼠咬肌线粒体出现水肿,基质密度降低,线粒体嵴减少,肌纤维微血管内出现充血性改变;睡眠剥夺9d组大鼠咬肌线粒体出现严重空泡性变,肌纤维微血管出现更为严重的充血性改变.结论:睡眠剥夺可导致咬肌肌纤维微血管充血性改变和线粒体损伤,这种变化随时间的延长而加重.     

睡眠剥夺对记忆功能及突触可塑性的影响

睡眠剥夺（SD）不仅会直接影响工作效率,还会随着疲劳程度的增加,对个体的记忆、注意力和学习等多种认知功能造成负面影响。在过去的几十年里,研究人员围绕SD对各种认知功能,尤其是对记忆功能的影响,开展了大量的研究。本文首先基于行为学研究综述了SD对记忆功能的影响,并进一步从结构和功能突触可塑性、兴奋性和抑制性神经递质水平以及相关突触蛋白信号表达等方面阐述了SD生理机制研究的最新进展。发现SD通过影响突触的活动变化（如树突棘密度、突触之间的连接和突触的兴奋和抑制的平衡）,从而对相关突触蛋白信号表达和下游信号通路进行调节,最终表现在行为学水平上。本文对SD影响记忆功能及其机制的研究进展进行综述,为今后进一步研究睡眠功能和相关机制,以及发展相关方法来改善SD引起的记忆功能缺陷提供参考。     

从睡眠剥夺树鼩（TBC）尿液提取内源性“睡眠因子”（sleep factor）的研究

本研究报道从睡眠剥夺（ＳＤ）４８—７２ｈ的灵长类原宗（ｐｒｉｍｉｔｉｖｅｓｔｏｃｋ）Ｔｕｐａｉａｂｅｌａｎｇｅｒｉｃｈｉｎｅｎｓｉｓ（ＴＢＣ）提取内源性“睡眠因子”（ｓｌｅｅｐｆａｃｔｏｒ）Ｓ２Ｃ和Ｓ４Ｂ。收集的尿液经超滤,清液冻干经ＳｅｐｈａｄｅｘＧ１５分离得到ＦｒａｃｔｉｏｎⅠ－Ⅴ。活性测定发现Ｆｒａｃｔｉｏｎ－Ⅲ（Ｓ２Ｃ）呈现显著δ－增强促眠效应。经ＳｅｐｈａｄｅｘＧ２５和ＳｅｐｈａｄｅｘＬＨ２０进一步净化的Ｓ４Ｂ也呈现显著δ－增强促眠效应。     

长期异相睡眠剥夺对大鼠能量代谢及血清甲状腺素水平的影响

目的：探讨长期异相睡眠剥夺对大鼠能量代谢及血清甲状腺素水平的影响。方法：采用小平台水环境法建立长期异相睡眠剥夺大鼠模型;检测其能量代谢变化;放射免疫法检测血清中甲状腺素水平。结果：睡眠剥夺后大鼠摄食量由（75.06±25.37）g/（d.kg）增加到（122.30±20.43）g/（d.kg）,体重由（360.89±43.01）g减轻到（295.97±37.95）g,体温由（37.62±1.12）℃先升高到（39.00±0.87）℃后又降低至（37.72±0.84）℃,基础代谢率由（1.69±0.36）mlO2/（g.h）增加到（2.40±0.09）mlO2/（g.h）与对照组相比差异显著（P〈0.05）;血清中游离三碘甲状腺原氨酸（FT3）水平由（3.38±0.88）pmol/L降低到（2.38±0.83）pmol/L,游离甲状腺素（FT4）由（14.62±3.62）pmol/L降低到（8.26±2.80）pmol/L与对照组相比差异显著（P〈0.05）。结论：长期异相睡眠剥夺可以显著影响大鼠的能量代谢和血清甲状腺素水平。     

不同时间睡眠剥夺对大鼠运动能力及谷氨酰胺的影响

目的：探索睡眠剥夺对大鼠运动能力及谷氨酰胺含量变化的影响,为睡眠剥夺后的运动训练等提供一定的实验依据。方法：将30只雄性SD大鼠按体重随机分安静对照组、0h睡眠剥夺力竭运动组（SDE）、24h SDE、48h SDE和72h SDE组（n=6）,采用轻柔刺激法建立睡眠剥夺模型和依据Bedford建立的大鼠运动模型。结果：24h SDE睡眠剥夺组与0h SDE组比较。大鼠后蹬跑时间明显长（P〈0．05）,48h SDE睡眠剥夺组和72h SDE睡眠剥夺与0h SDE睡眠剥夺组比较,后蹬跑时间显著性减少（P〈0．01）;24h SDE睡眠剥夺组与c组比较大鼠胸腺谷氨酰胺含量显著升高（P〈0．05）,48h SDE睡眠剥夺组和72h SDE睡眠剥夺组与C组比较大鼠胸腺谷氨酰胺含量降低（P〈0．01）;睡眠剥夺组与C组比较,血清谷氨酰胺含量的变化均具有高度显著性差异（P〈0．01）,睡眠剥夺24h后血清谷氨酰胺含量显著增多,却在睡眠剥夺48h、72h后血清谷氨酰胺含量明显下降。结论：①睡眠剥夺24h能提高大鼠运动能力,睡眠剥夺48h甚至是72h后大鼠运动能力开始降低。②睡眠剥夺24h后大鼠胸腺谷氨酰胺含量和血清谷氨酰胺含量升高,而睡眠剥夺48h后大鼠胸腺和血清的谷氨酰胺含量下降明显,睡眠剥夺72h后胸腺和血清谷氨酰胺含量显著性降低。     

快速眼动睡眠剥夺对大鼠恐惧消退再现的影响

目的：研究两种实验范式AAA和ABA（A、B表示不同场景）中快速眼动睡眠剥夺（RSD）对大鼠恐惧消退再现的影响。方法：1d大鼠适应环境;2d进行恐惧条件化;3d恐惧消退训练并进行RSD;4d进行恐惧消退再现检测。结果：AAA实验范式中,在恐惧消退再现检测阶段,0～6hRSD组大鼠的僵直水平显著高于对照组（P〈0．05）,其他阶段处理组与对照组大鼠的僵直水平都无显著性;ABA实验范式中,各阶段处理组与对照组大鼠的僵直水平都无显著性。结论：不同实验范式中RSD对恐惧消退影响不同,并且这种影响依赖于睡眠剥夺的时段。     

The effect of dopaminergic nigrostriatal system on sleep deprivation in rats

The analysis of the electrophysiological features of sleep-wakefulness cycle in Wistar rats for 9h after a 6h sleep deprivation was carried out. The delay of sleep rebound (since 2.5-3 h after deprivation) was found in the form of moderate increasing of slow-wave sleep and fast-wave sleep phases. According to these sleep-wakefulness cycle changes, a quantitative immunohistochemical study of tyrosine hydroxylase: a key enzyme of dopamine synthesis--and D1 and D2 receptors in nigro-striatal projections has been performed. After sleep, an elevation of D1 receptors immunoreactivity in caudate nucleus and reduction of tyrosine hydroxylase immunoreactivity in compact part of substancia nigra was found. After postdeprivation sleep, a decrease of D1 receptors immunoreactivity and increase of D2 receptors immunoreactivity in caudate nucleus together some increase of tyrosine hydroxilase immunoreactivity in substancia nigra compacta has been observed. These data can testify about active role of dopaminergic nigrostriatal system which provide at the same time with another neurotransmitters of the central nervous system the telencephalo-diencephalic interaction in sleep-wakefulness-sleep cycle.     

Phase advance is an actimetric correlate of antidepressant response to sleep deprivation and light therapy in bipolar depression

The combination of total sleep deprivation (TSD) and light therapy (LT) in bipolar depression causes rapid antidepressant effects, and its mechanism of action has been hypothesized to involve the enhancement of all of the monoaminergic systems targeted by antidepressant drugs (serotonin, dopamine, norepinephrine). It is still unknown if the clinical effects are paralleled by changes in biological rhythms. In a before/after design of a study of biological correlates of response, 39 inpatients affected by Type I Bipolar Disorder whose current depressive episode was without psychotic features were treated for one week with repeated TSD combined with morning LT. Wrist actigraphy was recorded throughout the study. Two-thirds of the patients responded to treatment (50% reduction in Hamilton Depression score). Responders showed an increase in daytime activity, phase-advance of the activity-rest rhythm of 57 min compared to the pre-treatment baseline, and reduced nighttime sleep. Non-responders did not show significant changes in the parameters of their activity-rest rhythm. Phase advance of the activity-rest rhythm is an actimetric correlate of the antidepressant response to TSD and LT in bipolar depression. Results are consistent with the known effects of sleep-wake manipulations and neurotransmitter function on the suprachiasmatic nucleus.     

Sleep deprivation suppresses adult neurogenesis: Clues to the role of sleep in brain plasticity

Sleep and Biological Rhythms - Sleep is hypothesized to play a critical role in facilitating brain growth and plasticity. Neurogenesis in the adult hippocampus is a recently established model of...     

Permissive role of adenosine A2A receptors on metabotropic glutamate receptor 5 (mGluR5)-mediated effects in the striatum

The metabotropic glutamate receptors 5 (mGlu5Rs) and the adenosine A2A receptors (A2ARs) have been reported to functionally interact in the striatum. The aim of the present work was to verify the hypothesis that the state of activation of A2A Rs could influence mGlu5R-mediated effects in the striatum. In electrophysiological experiments (extracellular recording in rat corticostriatal slices), the ability of the selective mGlu5R agonist CHPG to potentiate the reduction of the field potential amplitude induced by NMDA was prevented not only by the selective mGlu5R antagonist MPEP, but also by the selective A2AR antagonist ZM 241385. Analogously, the application of CHPG potentiated NMDA-induced toxicity (measured by LDH release) in cultured striatal neurons, an effect that was abolished by both MPEP and ZM 241385. Finally, the A2AR agonist CGS 21680 potentiated CHGP effects, an action that was reproduced and abolished, respectively, by forskolin (an activator of the cAMP/protein kinase A, PKA, pathway) and KT 5720 (a PKA inhibitor). The results indicate that A2ARs exert a permissive role on mGlu5R-induced effects in the striatum. Such an interaction may represent an additional target for the development of therapeutic strategies towards striatal disorders.     

The effect of the removal of the epiphysis on the antidepressive properties of paradoxical sleep deprivation in rats]

After REM sleep deprivation antidepressant shifts in forced swimming with increase of time of immobility and decrease of rhythmical index of depression were observed. Pinealectomy did not remove, but attenuated these behavioural changes.     

Enzymes of adenosine metabolism in the brain: diurnal rhythm and the effect of sleep deprivation

Adenosine plays a role in promoting sleep, an effect that is thought to be mediated in the basal forebrain. Adenosine levels vary in this region with prolonged wakefulness in a unique way. The basis for this is unknown. We examined, in rats, the activity of the major metabolic enzymes for adenosine - adenosine deaminase, adenosine kinase, ecto- and cytosolic 5'-nucleotidase - in sleep/wake regulatory regions as well as cerebral cortex, and how the activity varies across the day and with sleep deprivation. There were robust spatial differences for the activity of adenosine deaminase, adenosine kinase, and cytosolic and ecto-5'-nucleotidase. However, the basal forebrain was not different from other sleep/wake regulatory regions apart from the tuberomammillary nucleus. All adenosine metabolic enzymes exhibited diurnal variations in their activity, albeit not in all brain regions. Activity of adenosine deaminase increased during the active period in the ventrolateral pre-optic area but decreased significantly in the basal forebrain. Enzymatic activity of adenosine kinase and cytosolic-5'-nucleotidase was higher during the active period in all brain regions tested. However, the activity of ecto-5'-nucleotidase was augmented during the active period only in the cerebral cortex. This diurnal variation may play a role in the regulation of adenosine in relationship to sleep and wakefulness across the day. In contrast, we found no changes specifically with sleep deprivation in the activity of any enzyme in any brain region. Thus, changes in adenosine with sleep deprivation are not a consequence of alterations in adenosine enzyme activity.