BACKGROUND:Sudden infant death syndrome (SIDS) occurs predominantly during sleep between 2 and 6 months of age, suggesting impaired maturation of arousal pathways. The neurobiological mechanisms involved remain unclear. We investigated the role of wake-promoting Orexin (Ox) and Histamine (HA) neurons in SIDS. METHODS:Cerebrospinal fluid (CSF) Ox levels were measured in 61 living controls and 70 Sudden Unexpected Death Infants (SUDI: 38 SIDS, 32 explained deaths (ED)). HA and tele-methylhistamine (t-MeHA) were analyzed in an additional 46 SUDI (34 SIDS, 12 ED) and 42 controls. Immunohistochemistry was performed on hypothalamic tissue from 11 SIDS and 8 ED cases to quantify Ox and HA neuron numbers. RESULTS:CSF Ox levels did not differ overall between groups but were higher in SUDI infants aged 2-6 months. HA and t-MeHA levels were elevated in SUDI, likely reflecting postmortem release. Ox neuron numbers were increased in rostral hypothalamic region in SIDS compared with EDs, whereas HA neuron numbers were unchanged. CONCLUSIONS:SIDS is associated with increased Ox neuronal activity during the peak risk period, possibly reflecting a homeostatic upregulation in response to arousal deficit or repeated stress or hypoxia, while the role of HA system remains to be clarified with more sensitive biomarkers. IMPACT:First study evaluating orexin and histamine systems in SIDS using CSF and postmortem brain tissue. Identifies elevated orexin activity in SIDS infants, particularly in the 2-6 month risk window. No evidence to date for direct histamine involvement; need for more sensitive biomarkers. Suggests orexin system as a potential biomarker for SIDS risk stratification. Highlights the importance of combined neurobiological approaches for prevention.

Lavender essential oil (LEO), extracted from the flowers and upper parts of the lavender plant, has attracted considerable interest in the field of aromatherapy due to its anxiolytic, antidepressant, and hypnotic properties. However, the mechanisms underlying these effects of LEO remain inadequately elucidated, presenting challenges for its clinical application and promotion. This review aims to systematically analyze existing studies from a biological perspective to clarify the role and potential mechanisms of LEO in the contexts of anxiety, depression, and insomnia. The findings indicate that LEO exhibits anxiolytic effects by enhancing GABA receptor binding, increasing serotonin levels in the synaptic cleft, inhibiting glutamate release and its receptor interactions, and suppressing acetylcholine release at the neuromuscular junction. The antidepressant properties of LEO are attributed to its promotion of neurogenesis in the hippocampus, inhibition of inflammatory responses, and exertion of antioxidant effects. Furthermore, LEO has been demonstrated to possess hypnotic effects by elevating levels of melatonin and serotonin, reducing c-Fos expression in the prefrontal cortex, ventral hippocampus, and amygdala, and modulating GABAergic neurons in the central amygdala. These findings contribute to a deeper understanding of the biological effects of LEO and provide a substantial theoretical foundation for its clinical application.

Plateau zokors (Eospalax baileyi), endemic to the Qinghai-Tibet Plateau (QTP), are solitary subterranean rodents that spend their lifespan within underground burrows. Although the activity rhythms of the plateau zokors have been slightly documented, their sleep-wake patterns and seasonal variations remain unclear. Here, we investigated the sleep-wake patterns of wild-caught plateau zokors during spring and autumn using polysomnographic (PSG) recordings in the lab, and compared the findings with those of Sprague-Dawley (SD) rats. We found that plateau zokors exhibit three clearly distinguishable brain states: wakefulness (W), non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Under complete darkness in spring, they showed rhythmic-like activity. Compared with daytime periods, they spent significantly more time in wakefulness (398.88 ± 15.02 min vs. 320.55 ± 23.69 min, P < 0.05), and less time both in NREM sleep (257.32 ± 11.28 min vs. 312.23 ± 18.18 min, P < 0.05) and REM sleep (63.80 ± 6.63 min vs. 87.22 ± 7.27 min, P < 0.05) during the nocturnal period (local time). Although the plateau zokors in autumn did not exhibit significant rhythmic-like activity, they showed higher levels of wakefulness in the awake state and shallower sleep during sleep. Notably, plateau zokors had longer and more stable REM sleep compared to SD rats. These findings provide new empirical evidence for adaptive strategies in sleep ecophysiology and help reveal the functions and evolutionary strategies of sleep.

STUDY OBJECTIVES:Ponto-geniculo-occipital (PGO) waves are a hallmark feature of paradoxical sleep (PS), emerging just before PS onset during the transition from slow-wave sleep (SWS) to PS (TSWS-PS) and persisting throughout the PS phase in adult cats. These waves are considered a biomarker for the maturation of PS. However, their developmental trajectory in mammals remains poorly understood. This study investigated the emergence and maturation of PGO waves during PS in developing kittens. METHODS:Electrodes were stereotaxically implanted into the lateral geniculate nucleus, accurately localized using magnetic resonance imaging. Recording included cortical electroencephalogram, nuchal muscle activity, PGO waves, and rapid eye movements (REMs). RESULTS:Despite the presence of abundant PS and frequent muscle twitches accompanied by REMs in neonatal kittens, PGO spikes were first detected at postnatal day (PND) 16, with an average onset at PND 19. Initially, these waves appeared with lower density and amplitude during the TSWS-PS and PS phases. Over the following weeks, PGO wave density and amplitude increased, along with prolonged durations during both TSWS-PS and PS. Type I waves (singlet and bigeminy) predominated during TSWS-PS, while type II waves (clusters) were more frequent during PS. The proportion of type II waves and their co-occurrence with REMs increased with age. The adult-like pattern of PGO waves was fully established by PND 50. CONCLUSIONS:The emergence and maturation of PGO waves during PS are closely linked to the development of the sleep-wake cycle and may play a role in learning and memory processes.

ETHNOPHARMACOLOGICAL RELEVANCE:The use of lavender as sleep aid or hypnotic agent can be traced back as early as ancient Romans and Greeks. Yet, objective experimental data on whether and how lavender enhances sleep duration or/and sleep quality remain lacking. AIM OF THE STUDY:We aimed to characterize the sleep-wake regulating effects of lavender in the mouse and to demonstrate the brain targets and neural circuits involved. MATERIALS AND METHODS:A self-made precise odor delivery system combined with chronic polysomnographic recordings was employed to assess the sleep-wake effects of inhalation with lavender essential oil (LEO, extracted from lavender) and its different constituents during the light and dark phases in free-moving C57BL/6J mice. Neuroviral labeling, in situ hybridization and pharmacogenetics were combined to identify the neural circuits and targets involved. Finally, an insomniac model of DL-4-Chlorophenylalanine (PCPA)-treated mice was established to examine the sleep-inducing potential of LEO. RESULTS:We found that inhalation of LEO with a concentration at 25.0% during the light (inactive) phase significantly shortened the latency to non-rapid eye movement (NREM) sleep, increased the total amount of NREM sleep at the expense of wakefulness (W), and enhanced cortical EEG slow wave activities, notably delta power spectra density. We further identified linalool, d-limonene, 1,8-cineole, linalyl acetate and terpinene-4-ol as the major effective sleep-promoting monomer components. Importantly, we found that LEO no longer produced any of the above sleep-promoting effect following either nasal injection of zinc sulfate which interrupts the olfactory pathway, or pharmacogenetics silencing of central amygdala GABAergic neurons. Finally, LEO reestablished NREM sleep with short latency in PCPA-treated insomniac mice, effects comparable with those induced by a potent sedative diazepam. CONCLUSIONS:We have characterized the quantitative and qualitative sleep-promoting effects of LEO and its effective components via the olfactory pathway and central amygdala GABA neuronal targets. The hypnotic property of LEO is reinforced by its ability to restore sleep in insomnia. Our study thus establishes a neurobiological basis for aromatherapy of sleep disorders using lavender.

Rapid eye movement (REM) sleep is the main sleep correlate of dreaming. Ponto-geniculo-occipital (PGO) waves are a signature of REM sleep. They represent the physiological mechanism of REM sleep that specifically limits the processing of external information. PGO waves look just like a message sent from the pons to the lateral geniculate nucleus of the visual thalamus, the occipital cortex, and other areas of the brain. The dedicated visual pathway of PGO waves can be interpreted by the brain as visual information, leading to the visual hallucinosis of dreams. PGO waves are considered to be both a reflection of REM sleep brain activity and causal to dreams due to their stimulation of the cortex. In this review, we summarize the role of PGO waves in potential neural circuits of two major theories, i.e., (1) dreams are generated by the activation of neural activity in the brainstem; (2) PGO waves signaling to the cortex. In addition, the potential physiological functions during REM sleep dreams, such as memory consolidation, unlearning, and brain development and plasticity and mood regulation, are discussed. It is hoped that our review will support and encourage research into the phenomenon of human PGO waves and their possible functions in dreaming.

The ontogenetic sleep hypothesis suggested that rapid eye movement (REM) sleep is ontogenetically primitive. Namely, REM sleep plays an imperative role in the maturation of the central nervous system. In coincidence with a rapidly developing brain during the early period of life, a remarkably large amount of REM sleep has been identified in numerous behavioral and polysomnographic studies across species. The abundant REM sleep appears to serve to optimize a cerebral state suitable for homeostasis and inherent neuronal activities favorable to brain maturation, ranging from neuronal differentiation, migration, and myelination to synaptic formation and elimination. Progressively more studies in Mammalia have provided the underlying mechanisms involved in some REM sleep-related disorders (e.g., narcolepsy, autism, attention deficit hyperactivity disorder (ADHD)). We summarize the remarkable alterations of polysomnographic, behavioral, and physiological characteristics in humans and Mammalia. Through a comprehensive review, we offer a hybrid of animal and human findings, demonstrating that early-life REM sleep disturbances constitute a common feature of many neurodevelopmental disorders. Our review may assist and promote investigations of the underlying mechanisms, functions, and neurodevelopmental diseases involved in REM sleep during early life.

甘丙肽(GAL)及其受体(GalRs)广泛分布于中枢神经系统,参与多种生理功能调节.下丘脑前部腹外侧视前核(VLPO) 80％神经元含GAL并与γ-氨基丁酸共存,发出下行投射至多个觉醒核团,抑制结节乳头体核、中缝背核和蓝斑核神经元活动而促进睡眠.本研究回顾GAL-GalRs系统在中枢神经系统的发现,聚焦多项利用神经示踪、神经药理学、分子生物学、化学遗传和光遗传学等方法研究进展,证明VLPO GAL能神经元调控生理条件下慢波睡眠的产生和维持以及参与阿尔茨海默症、焦虑、抑郁、癫痫和成瘾等疾病及伴随睡眠障碍的机制,总结性地提出尚未清晰的问题和研究方向.

睡眠觉醒发育与脑发育密切相关,多数动物睡眠觉醒节律发育规律与人类相似,由脑内生物钟、睡眠觉醒中枢和内平衡稳态等因素调节.成人的觉醒与睡眠呈昼夜节律性出现,整夜睡眠20％为快动眼(REM)睡眠,80％为非快动眼(NREM)睡眠.NREM-REM睡眠转换周期为90～110 min,表现为次昼夜节律.足月新生儿觉醒与睡眠昼夜均匀分布,睡眠常以REM睡眠起始,REM与NREM睡眠各占50％,转换周期为50～60 min;3月龄开始显现昼夜节律分布,睡眠周期以NREM睡眠起始,10岁后NREM-REM睡眠周期呈现近似成年次昼夜节律水平.睡眠与觉醒的昼夜节律及次昼夜节律的发育参与个体的生理和心理发育过程,了解睡眠觉醒节律调控及发育,为理解脑发育和新生儿睡眠节律异常导致的疾病奠定理论基础.

The thalamus is the gate of the cerebral cortex, the ultimate target for the neural networks controlling behavioral states and cognitive functions. According to the reticular theory initially proposed by Moruzzi and Magoun, excitatory inputs from large reticular zones of the brainstem via widespread intra-and extra-thalamocortical systems finally activate the cerebral cortex to cause generalized cortical

Intracerebroventricular injection of NPS reduces the duration of the ketamine- or thiopental-induced loss of the righting reflex in rats. But the specific EEG activities are unknown. We therefore sought to examine the effects of the NPS-NPSR system on anesthetic-induced characteristics of EEG power spectra and sleep-wake profiles. NPS alone or together with an NPSR antagonist was injected intracerebroventricularly, whereas the propofol (50mg/kg) or ketamine (100mg/kg) was administrated intraperitoneally. NPS (1 or 2nmol) significantly reduced the amount of propofol-induced EEG delta activity and slow wave states (SWS). NPS (1 or 5nmol) significantly reduced the amount of ketamine-induced SWS and EEG delta activity. Cortical EEG power spectral analysis showed that, in saline-pretreated rats, propofol induced a marked increase in delta (0.5-4Hz) activity, decrease in theta (4.5-8.5Hz) activity, and decrease in high frequency activity (14.5-60Hz), while, in rats pretreated with 1nmol of NPS, the duration of delta activity was reduced, while its spectral pattern was not changed. Whereas injection of ketamine into saline-pretreated rats induced a marked increase in delta (0.5-4Hz) activity, a moderate increase in theta (4.5-8.5Hz) activity, and a marked decrease in high frequency (14.5-60Hz) activity. However, delta activity was reduced while theta activity increased under pretreatment with 1nmol of NPS. The inhibitory effect of NPS on anesthetic-induced SWS was characterized by a reduced SWS episode duration with no significant change in either episode number or latency to SWS. [D-Val5]NPS, an NPSR antagonist (20nmol), significantly attenuated the arousal-promoting effect of 1nmol of NPS, but had no effect on SWS when injected alone. We speculate that NPS significantly reduces anesthetic-induced SWS and EEG slow activity by selective activation of the NPSR, which, in turn, would trigger subsequent arousal pathways.

Background: Our purpose was to investigate the relationship between oxygen saturation (SpO(2)) and dynamic interstitial glucose level (IGL) in patients with obstructive sleep apnea (OSA) along with type 2 diabetes mellitus (T2DM), and to investigate the potential mechanisms thereof.Materials and Methods: A total of 130 patients with OSA and T2DM underwent polysomnography and oral glucose tolerance tests at the Sleep Medicine Center. Using the lowest (L) SpO(2)% tested, patients were divided into mild, moderate and severe LSpO(2) groups. Polysomnography and continuous glucose monitoring systems were used to analyze the altered pattern of SpO(2) and dynamic IGL in the 3 groups.Results: LSpO(2) during sleep in patients with OSA and T2DM stimulated an increase in IGL. The moderate and severe levels were represented by IGL 45 and IGL 30, respectively. The average nocturnal and peak IGL after LSpO(2) in the severe group were significantly higher than in the mild and moderate groups. Stepwise multiple regression analysis showedt hat the body mass index (beta = 0.301, P < 0.001), homeostatic model assessment of insulin resistance (beta = 0.260, P < 0.001), apnea-hypopnea index (beta = 0.309, P < 0.001), average SpO(2) (beta = -0.423, P = 0.008), LSpO(2) (beta = -0.369, P < 0.001) and microarousal index (beta = 0.335, P = 0.044) were probably related to nocturnal IGL in patients with OSA along with T2DM.Conclusions: Severe and moderate OSA with T2DM is marked by a delayed IGL peak following LSpO(2). Nocturnal hypoxemia causes hyperglycemia in patients with OSA along with T2DM.

Botulinum toxin type A (BTX-A) selectively cleaves synaptosomal-associated protein of 25 kDa (SNAP-25) and results in inhibition of the fusion of synaptic vesicles containing neurotransmitters with the presynaptic membrane to undergo exocytosis and release. The aim of this study was to investigate whether BTX-A inhibited the pyloric smooth muscle contractility induced by acetylcholine (ACh) after BTX-A-mediated cleavage of SNAP-25 antagonized by toosendanin (TSN). Three groups of rat pyloric muscle strips were studied in vitro. All strips were allowed to equilibrate for 52 min under a basal loading tension of 1 g in Krebs solution and spontaneous contractile waves were recorded as their own controls before adding each drug. According to experimental protocols, 100 μM ACh, 1 μM atropine, 29.6 μM TSN and 10 U/ml BTX-A was added, respectively. BTX-A directly inhibited pyloric spontaneous contraction and ACh-induced contractile response. Addition of 10 U/ml BTX-A still inhibited pyloric smooth muscle contractility following incubation of TSN, while subsequent administration of 100 μM ACh had no effect. BTX-A inhibits pyloric smooth muscle contractility in our study suggesting BTX-A inhibits not only ACh release from cholinergic nerves but also muscarinic cholinergic muscular transmission.

OBJECTIVETo investigate the characteristic of dynamic glucose level in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients with newly diagnosed type 2 diabetes mellitus (T2DM) and to evaluate the effect of continuous positive airway pressure (CPAP) treatment on the glucose level.METHODSA total of 65 cases of patients with T2DM who were newly diagnosed by oral glucose tolerance test (OGTT) were enrolled from April 2014 to April 2015 in Gansu Provincial Hospital, and divided into simple T2DM group (n=30) and OSAHS with T2DM group (n=35) according to aponea-hypopnea index (AHI) which was monitored by polysomnography (PSG). Their general clinical data were collected, and glucose level of different periods was monitored by continuous glucose moitoring system (CGMS). Changes of glucose level were compared between two groups before and after CPAP treatment.RESULTSAge, gender proportion, BMI, smoking and drinking history, glycosylated hemoglobin (HbA1c) and blood lipid profile had no significantly difference between two groups. Longer neck circumstance and higher waist-hip ration (WHR), higher systolic blood pressure and diastolic blood pressure, higher fasting plasma glucose (FPG) [(9.4 ± 3.2) vs (7.3 ± 2.1) mmol/L, P=0.028] and fasting insulin (FINS) [(19.2 ± 8.7) vs (11.1 ± 4.7) mU/L, P=0.044] level, more serious homeostasis model assessment insulin resistance (HOMA-IR) were found in OSAHS patients with T2DM when compared to patients in simple T2DM group. The average dynamic glucose level of 24 hours, daytime, nocturnal and sleep time in OSAHS with T2DM group were higher than that in the simple T2DM group (all P<0.05). The alarming times when the average dynamic glucose level of nocturnal time was more than 0.1 mmol·L⁻¹·min⁻¹ in T2DM with OSAHS was more than that in control group (P=0.001). After treatment of CPAP, the level of AHI [(5.9 ± 3.6) vs (56.7 ± 11.4) times/h, P<0.001], average dynamic glucose level of 24 hours, day, nocturnal and sleep time were obviously decreased (all P<0.05); lowest saturation oxygen (LSpO₂) was significantly increased [(92.3 ± 3.7)% vs (81.5 ± 20.2)%, P<0.001]; the alarming times and HOMA-IR were obviously decreased (P=0.019, 0.043). According to multiple linear regression analysis, the AHI (β=0.736, P<0.001) in OSAHS with T2DM group was positively related to the average dynamic glucose level during sleep time, but the LSpO₂(β=-0.889, P<0.001) was negatively correlated.CONCLUSIONSOSAHS patients with newly diagnosed T2DM have higher glucose level than that in simple T2DM patients, and CPAP therapy can obviously decrease the glucose level in newly diagnosed T2DM patients with OSAHS. AHI and LSpO₂may influence the average dynamic glucose level during sleep time.

A decrease in pyloric myoelectrical activity and pyloric substance P (SP) content following intrasphincteric injection of botulinum toxin type A (BTX-A) in free move rats have been demonstrated in our previous studies. The aim of the present study was to investigate the inhibitory effect of BTX-A on rat pyloric muscle contractile response to SP in vitro and the distributions of SP and neurokinin 1 receptor (NK1R) immunoreactive (IR) cells and fibers within pylorus. After treatment with atropine, BTX-A (10 U/mL), similar to [D-Arg1, D-Phe5, D-Trp7,9, Leu11]-SP (APTL-SP, 1 μmol/L) which is an NK1R antagonist, decreased electric field stimulation (EFS)-induced contractile tension and frequency, whereas, subsequent administration of APTL-SP did not act on contractility. Incubation with BTX-A at 4 and 10 U/mL for 4 h respectively decreased SP (1 μmol/L)-induced contractions by 26.64% ± 5.12% and 74.92% ± 3.62%. SP-IR fibers and NK1R-IR cells both located within pylorus including mucosa and circular muscle layer. However, fewer SP-fibers were observed in pylorus treated with BTX-A (10 U/mL). In conclusion, BTX-A inhibits SP release from enteric terminals in pylorus and EFS-induced contractile responses when muscarinic cholinergic receptors are blocked by atropine. In addition, BTX-A concentration- and time-dependently directly inhibits SP-induced pyloric smooth muscle contractility.

[ABSTRACT]OBJECTIVETo assess the sleep body position's effects on AHI and ODI during sleep in obstructive sleep apnea hypopnea syndrome (OSAHS) patients with different severity.METHODSThe clinical data of 113 subjects who had been diagnosed OSAHS or normal by polysomnography (PSG) between 2013 and 2014 in our department were retrospectively studied. They were divided into normal control group (AHI<5/h, 41 patients), mild to moderate OSAHS group (5/h30/h, 40 patients). PSG data of AHI and ODI in different body position in each group were further analyzed.RESULTSIn normal group, The AHI and ODI in supine position were significantly higher than that in the left or right lateral position, and the difference between the left and right lateral position was not significant. In the mild to moderate OSAHS group, the AHI and ODI in supine were higher than that in the left lateral position slightly, while the data in supine was higher than that in the right lateral position significantly. In the severe group, the data between the supine and the left lateral position was not statistically different, while the supine position data was higher compared with that of the right lateral position. CONCLUSIONAHI and ODI were higher in supine position than that in lateral position, while the AHI and ODI in right lateral position is higher than that in left lateral position in OSAHS patients with different severity. The ODI and AHI are consistent in reflecting the severity of the OSAHS.

目的：对比自制磨牙大面积缺损修复成型模与传统成形片的临床效果，评估其应用于临床的可行性。方法在该装置帮助下，以银汞合金为充填物修复缺损磨牙（n=120），统计成功率，治疗后充填物的脱落数以及咀嚼效率，对比分析修复效果。结果成型模组修复成功率84.93%，成形片组为68.33%，（P=0.01）；成型模组咀嚼效率增加（8.32±4.31），成形片组咀嚼效率增加（2.95±4.1），（P=0.022）；成型模组填充体脱落数为2，成形片组填充体脱落数为24，（P=0.002）。结论与传统的成形片修复方法相比较，自制成型模在成功率以及咀嚼效率的恢复上有明显优势，但操作程序繁琐，有待改进。

新发现神经肽S (NPS)及其受体(NPSR)构成一新的内源性神经调节系统,NPS-NPSR系统被认为是中枢新的觉醒系统参与睡眠觉醒周期的生理与病理过程.近期研究证明侧脑室注射NPS引起大鼠脑电高频(14.5～60 Hz)活动增强为特征的觉醒时间增加,同时抑制脑电δ波和θ波为特征的慢波睡眠(SWS)和异相睡眠或称为快动眼睡眠(PS/REMS);NPSR拮抗剂[D-Cys(tBu)5] NPS引起大鼠觉醒减少,SWS增加,而不影响PS/REMS. NPSR rs324981单核苷酸多态性和Asn/Ile 107 NPSR多态性与人类的生理性睡眠调节密切相关.机制研究揭示下丘脑结节乳头体核(TMN)91.5％组胺能神经元表达NPSR,TMN注射0.1 nmoL NPS引起大鼠觉醒时间,比侧脑室注射1nmoL NPS引起大鼠觉醒时间显著延长,该作用可分别被NPSR、组胺受体H1R和组胺受体H2R拮抗剂所拮抗,提示NPS神经元投射TMN经NPSR介导激活组胺能神经元是NPS-NPSR调节睡眠觉醒的重要通路.另外,证据表明NPS抗焦虑与抑郁引起睡眠紊乱.为此,揭示NPS能神经元投射途径、作用靶点与突触后神经元作用模式,发现NPSR高效激动剂及拮抗剂将成为今后工作重点.