Neurobiology of Sleep and Circadian Rhythms最新文献

The circadian clock, which generates the internal daily rhythm largely mediated through release of melatonin, can be disrupted in various ways. Multiple factors result in a disruption of the circadian cycle in the clinical context, of interest are anti-cancer drugs such as cisplatin. Cisplatin modulates the circadian clock through two mechanisms: 1) the circadian clock control of DNA excision repair and 2) the effect of circadian clock disruption on apoptosis. Cisplatin can stimulate multiple classified molecules, including DNA repair factors, DNA damage recognition factors and transcription factors in drug resistance and cisplatin-induced signal transduction. These factors interact with each other and can be transformed by DNA damage. Hence, these molecular interactions are intimately involved in cell proliferation and damage-induced apoptosis. Cisplatin has a dual-effect on circadian genes: upregulation of CLOCK expression causes an increase in proliferation but upregulation of BMAL1 expression causes an increase in apoptosis. Therefore, the interference of circadian genes by cisplatin can have multiple, opposing effects on apoptosis and cell proliferation, which may have unintended pro-cancer effects. Melatonin and intracellular Ca²⁺ also have a dual-effect on cell proliferation and apoptosis and can disrupt circadian rhythms.

Recently, it has been suggested that sleep problems in autism spectrum disorder (ASD) not only are associated symptoms, but may be deeply related to ASD pathogenesis. Common clinical practice relating to developmental disorders, has shown that parents of children with ASD have often stated that it is more difficult to raise children in the neonatal period because these children exhibit sleep problems. This study investigated the possibility that abnormal neonatal sleep-wake rhythms are related to future ASD development.

We administered questionnaires to assess parent(s) of children with ASD and controls. A retrospective analysis was conducted among 121 children with ASD (94 male and 27 female children) recruited from the K-Development Support Center for Children (K-ASD), 56 children with ASD (40 male and 16 female children) recruited from the H-Children's Sleep and Development Medical Research Center (H-ASD) and 203 children (104 male and 99 female children) recruited from four nursery schools in T-city (control).

Irritable/over-reactive types of sleep-wake rhythms that cause difficulty in raising children, such as 1) frequently waking up, 2) difficulty falling asleep, 3) short sleep hours, and 4) continuous crying and grumpiness, were observed more often in ASD groups than in the control group. Additionally, the number of the mothers who went to bed after midnight during pregnancy was higher in the ASD groups than in the control group.

Sleep-wake rhythm abnormalities in neonates may be considerable precursors to future development of ASD. Formation of ultradian and postnatal circadian rhythms should be given more attention when considering ASD development. Although this is a retrospective study, the results suggest that a prospective study regarding this issue may be important in understanding and discovering intervention areas that may contribute to preventing and/or properly treating ASD.

Sleep deprivation (SD) and fatigue have detrimental effects on performance in operational settings. Few studies have investigated the cumulative effects of SD and fatigue on performance under heavy workload demands. Therefore, we investigated the efficacy of multiple repeated doses of caffeine as a countermeasure to SD and fatigue during 77 h total SD (TSD) during the early morning hours. Twenty-three males and females, 18 – 35 years of age, who identified as moderate caffeine consumers completed the Psychomotor Vigilance Task (PVT) 141 times during the experimental test period. Caffeine was administered in a multi-dose paradigm over three nights without sleep. Participants received either caffeine (200 mg) or placebo at the beginning of each 2-h test block from 0100 – 0900 (800 mg total per night). While PVT speed declined for both groups across all 3 nights, the caffeine group consistently out-performed the placebo group. Caffeine maintained attentiveness (1-5 s lapses) on night 1, but this advantage was lost on nights 2 and 3. Caffeine outperformed placebo for responsive lapses (5-9 s lapses) across all three nights, but caffeine performance was still notably worse than at baseline. Prolonged non-responsive lapses (beyond 10 s) were only reduced by caffeine on night 2. Caffeine was more effective than placebo across all nights at sustaining completion speed of a complex motor sequence task and a manual coordination task. Essentially, caffeine is an effective countermeasure for SD, as it mitigates declines in speed and failures to respond, and sustains motor planning and coordination. However, caffeine does not restore normal functioning during SD and cannot be considered as a replacement for sleep.

Purpose

We reported one patient infected with acute respiratory syndrome coronavirus-2 (SARS-CoV-2) presented with sleep disorders; insomnia and restless leg syndrome.

Methods

Patient data were obtained from medical records from Al-Raghy Isolation Hospital in Assuit University.

Results

A 49-year-old female patient presented with insomnia and restless leg syndrome associated with anosmia, ageusia. Three days before, she had developed a cough, malaise and athenia, headache, arthralgia, myalgia affecting mainly upper limbs, diarrhea and a fever followed by tachypnea. The naso-oropharyngeal swab test for coronavirus disease 2019 (COVID-19) by qualitative real-time reverse-transcriptase–polymerase-chain-reaction assay was positive. The patient was treated with Oseltamivir 75mg and clarithromycin 500 mg (12 hourly for each respectively) for 10 days with paracetamol. Two weeks later, the patient made a complete neurological and respiratory recovery.

Conclusion

Our case highlighted the rare occurrence of restless leg syndrome and insomnia during the COVID-19 pandemic. The era of sleep disorders spectrum in patients with COVID-19 remains to be characterized suggesting a frightening scientific association between COVID-19 and neuropsychiatric illness.

The circadian and endocrine systems influence many physiological processes in animals, but little is known on the ways they interact in insects. We tested the hypothesis that juvenile hormone (JH) influences circadian rhythms in the social bumble bee Bombus terrestris. JH is the major gonadotropin in this species coordinating processes such as vitellogenesis, oogenesis, wax production, and behaviors associated with reproduction. It is unknown however, whether it also influences circadian processes. We topically treated newly-emerged bees with the allatoxin Precocene-I (P-I) to reduce circulating JH titers and applied the natural JH (JH-III) for replacement therapy. We repeated this experiment in three trials, each with bees from different source colonies. Measurements of ovarian activity suggest that our JH manipulations were effective; bees treated with P-I had inactive ovaries, and this effect was fully recovered by subsequent JH treatment. We found that JH augments the strength of circadian rhythms and the pace of rhythm development in individually isolated newly emerged worker bees. JH manipulation did not affect the free-running circadian period, overall level of locomotor activity, sleep amount, or sleep structure. Given that acute manipulation at an early age produced relatively long-lasting effects, we propose that JH effects on circadian rhythms are mostly organizational, accelerating the development or integration of the circadian system.

Objectives

Depersonalization is characterized by feelings of detachment from reality and has been associated with anxiety and depression, both of which have a bi-directional relationship with sleep. To date, few studies have directly examined the potential relationship between sleep and depersonalization, which was the primary objective of our study.

Design/methods

A cross-sectional study of female, Emirati, university students (n = 100) was conducted. Participants completed the Pittsburgh Sleep Quality Index (PSQI), the Cambridge Depersonalization Scale (CDS) and the Hospital Anxiety and Depression Scale (HADS). Additionally, 36 of the 100 participants wore wrist actigraphy for two consecutive weekdays. Average sleep duration, and average sleep efficiency (SE; %) across the two nocturnal sleep episodes were calculated. Total number of sleep episodes were obtained from wrist actigraphy and sleep logs.

Results

A significant, positive relationship was observed between PSQI global score and CDS total score (r = 0.21, p = 0.04). Actigraphy-estimated average nocturnal sleep duration was not significantly associated with the CDS. Compared to nocturnal sleepers only, those who undertook daytime naps had almost three times the risk of meeting the criteria for depersonalization disorder (OR = 2.95, 95% CI: 1.04–8.41), after adjustment. For each 1% increase in SE a 23% decreased risk of depersonalization was observed (OR = 0.77, 95% CI: 0.61–0.96), after adjustment.

Conclusions

Sleep screening in young adults may help to ensure better detection and management of psychological health outcomes. Our findings need to be confirmed prospectively in larger samples and amongst different populations but reiterate the importance of sleep habits pertaining to mental health.

The response to a zeitgeber, particularly the light/dark cycle, may vary phenotypically. Phenotypic plasticity can be defined as the ability of one genome to express different phenotypes in response to environmental variation. In this opinion paper, we present some evidence that one of the most prominent effects of the introduction of electric light to the everyday life of humans is a significant increase in phenotypic plasticity and differences in interindividual phases of entrainment. We propose that the healthy limits of phenotypic plasticity have been surpassed in contemporary society.

Circadian rhythms evolved within single cell organisms and serve to regulate rest-activity cycles in most single-cell and multiple-cell organisms. In contrast, sleep is a network emergent property found in animals with a nervous system. Rhythms and sleep are much entangled involving shared regulatory molecules such as adenosine, ATP, cytokines, neurotrophins, and nitric oxide. These molecules are activity-dependent and act locally to initiate regulatory events involved in rhythms, sleep, and plasticity.

Traumatic brain injury (TBI) is a complex and costly worldwide phenomenon that can lead to many negative health outcomes including disrupted circadian function. There is a bidirectional relationship between the immune system and the circadian system, with mammalian coordination of physiological activities being controlled by the primary circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN receives light information from the external environment and in turn synchronizes rhythms throughout the brain and body. The SCN is capable of endogenous self-sustained oscillatory activity through an intricate clock gene negative feedback loop. Following TBI, the response of the immune system can become prolonged and pathophysiological. This detrimental response not only occurs in the brain, but also within the periphery, where a leaky blood brain barrier can permit further infiltration of immune and inflammatory factors. The prolonged and pathological immune response that follows TBI can have deleterious effects on clock gene cycling and circadian function not only in the SCN, but also in other rhythmic areas throughout the body. This could bring about a state of circadian desynchrony where different rhythmic structures are no longer working together to promote optimal physiological function. There are many parallels between the negative symptomology associated with circadian desynchrony and TBI. This review discusses the significant contributions of an immune-disrupted circadian system on the negative symptomology following TBI. The implications of TBI symptomology as a disorder of circadian desynchrony are discussed.