Insulin resistance induced by long-term sleep deprivation in rhesus macaques can be attenuated by Bifidobacterium.

Long-term sleep deprivation (SD) is a bad lifestyle habit, especially among specific occupational practitioners, characterized by circadian rhythm misalignment and abnormal sleep/wake cycles. SD is closely associated with an increased risk of metabolic disturbance, particularly obesity and insulin resistance. The incretin hormone, glucagon-like peptide-1 (GLP-1), is a critical insulin release determinant secreted by the intestinal L-cell upon food intake. Besides, the gut microbiota participates in metabolic homeostasis and regulates GLP-1 release in a circadian rhythm manner. As a commonly recognized intestinal probiotic, Bifidobacterium has various clinical indications regarding its curative effect. However, few studies have investigated the effect of Bifidobacterium supplementation on sleep disorders. In the present study, we explored the impact of long-term SD on the endocrine metabolism of rhesus monkeys and determined the effect of Bifidobacterium supplementation on the SD-induced metabolic status. Lipid concentrations, body weight, fast blood glucose, and insulin levels increased after SD. Furthermore, after 2 mo of long-term SD, the intravenous glucose tolerance test showed that the glucose metabolism was impaired and the insulin sensitivity decreased. Moreover, 1 mo of Bifidobacterium oral administration significantly reduced blood glucose and attenuated insulin resistance in rhesus macaques. Overall, our results suggested that Bifidobacterium might be used to alleviate SD-induced aberrant glucose metabolism and improve insulin resistance. Also, it might help in better understanding the mechanisms governing the beneficial effects of Bifidobacterium.NEW & NOTEWORTHY Our findings demonstrated that long-term sleep deprivation is closely associated with metabolic syndromes. Bifidobacterium administration showed a superior effect on insulin resistance caused by sleep deprivation. Overall, we provide prevention and treatment methods for long-term sleep deprivation, a bad lifestyle habit among specific occupational practitioners, such as irregular shift workers.

Glucose control upon waking is unaffected by hourly sleep fragmentation during the night, but is impaired by morning caffeinated coffee.

Morning coffee is a common remedy following disrupted sleep, yet each factor can independently impair glucose tolerance and insulin sensitivity in healthy adults. Remarkably, the combined effects of sleep fragmentation and coffee on glucose control upon waking per se have never been investigated. In a randomised crossover design, twenty-nine adults (mean age: 21 (sd 1) years, BMI: 24·4 (sd 3·3) kg/m2) underwent three oral glucose tolerance tests (OGTT). One following a habitual night of sleep (Control; in bed, lights-off trying to sleep approximately 23.00-07.00 hours), the others following a night of sleep fragmentation (as Control but waking hourly for 5 min), with and without morning coffee approximately 1 h after waking (approximately 300 mg caffeine as black coffee 30 min prior to OGTT). Individualised peak plasma glucose and insulin concentrations were unaffected by sleep quality but were higher following coffee consumption (mean (normalised CI) for Control, Fragmented and Fragmented + Coffee, respectively; glucose: 8·20 (normalised CI 7·93, 8·47) mmol/l v. 8·23 (normalised CI 7·96, 8·50) mmol/l v. 8·96 (normalised CI 8·70, 9·22) mmol/l; insulin: 265 (normalised CI 247, 283) pmol/l; and 235 (normalised CI 218, 253) pmol/l; and 310 (normalised CI 284, 337) pmol/l). Likewise, incremental AUC for plasma glucose was higher in the Fragmented + Coffee trial compared with Fragmented. Whilst sleep fragmentation did not alter glycaemic or insulinaemic responses to morning glucose ingestion, if a strong caffeinated coffee is consumed, then a reduction in glucose tolerance can be expected.

Normalization of disrupted clock gene expression in males with tetraplegia: a crossover randomized placebo-controlled trial of melatonin supplementation.

STUDY DESIGN: Crossover double blind, randomized placebo-controlled trial. OBJECTIVES: Circadian oscillators are located both in the brain and in peripheral organs. Melatonin, the main brain-derived hormone governing circadian variations, is highly associated with daylight patterns. However, in subjects with tetraplegia the melatonin levels are blunted. Here we studied peripheral oscillators in peripheral blood mononuclear cells (PBMCs) in males with tetraplegia by examining how exogenous melatonin may influence the expression of clock gene mRNAs. SETTING: Sunnaas Rehabilitation Hospital, Nesoddtangen, Norway. METHODS: Six males with tetraplegia received 2 mg of melatonin or placebo 4 days before the study period. We also included six able-bodied men sleeping or kept awake during the night. Plasma samples were collected four times during a 24-h period. The mRNA expression levels of the clock genes PER1, PER2, BMAL1, and REV-ERBα were quantified in PBMCs using quantitative RT-PCR. RESULTS: The mRNA expression levels of PER-1 and -2 and REV-ERBα were increased at 04:00 h compared with the able-bodied controls (p < 0.05). Melatonin supplementation changed mRNA peak-time toward the time of supplementation. CONCLUSIONS: Several peripheral clock genes displayed distorted expression levels in tetraplegia. Supplementation with melatonin changed the mRNA expression levels of these genes toward those observed among able-bodied. SPONSORSHIP: Financial support was provided from the Throne Holst Foundation, Sunnaas Rehabilitation hospital and the University of Ferrara (FAR2016).

Stem Cell Factor (SCF) is a putative biomarker of antidepressant response.

Growth factors involved in neurogenesis and neuroplasticity could play a role in biological processes that drive depression recovery. Combined total sleep deprivation and morning light therapy (TSD + LT) can acutely reverse depressive symptoms, thus allowing to investigate the neurobiological correlates of antidepressant response. We tested if changes on plasma levels of Brain Derived Neurotrophic Factor (BDNF), S100 calcium binding protein B (S100-B), Stem Cell Factor (SCF), Insulin-like Growth Factor-Binding Protein 2 (IGFBP-2), Epidermal Growth Factor (EGF), Platelet-Derived Growth Factor-BB (PDGF-BB), and Vascular Endothelial Growth Factor (VEGF) are associated with response to TSD + LT in 26 inpatients affected by a major depressive episode in the course of bipolar disorder. Regional grey matter (GM) volumes were assessed at baseline, and BOLD fMRI neural responses to a moral valence decision task were recorded before and after treatment. 61.5 % of patients responded to treatment. SCF plasma levels increased significantly more in responders, and correlated with GM volumes in frontal and parietal cortical areas. The pattern of change of SCF also associated with both GM volumes and changes of BOLD fMRI neural responses in the anterior cingulate and medial prefrontal cortex. SCF is both a hematopoietic growth factor and a neurotrophic factor, involved in neuron-neuron and neuron-(micro) glia interactions, fostering neuronal growth and an anti-inflammatory milieu. We correlated SCF levels with antidepressant response and with functional and structural MRI measures in cortical areas that are involved in the cognitive generation and control of affect. SCF may be a candidate growth factor that contributes to neurotrophic and immune effects that are involved in the process of remission/recovery from depression.

Plant-derived nanoparticle treatment with cocc 30c ameliorates attention and motor abilities in sleep-deprived rats.

Sleep is an essential physiological process that underlies crucial cognitive functions as well as emotional reactivity. Thus, sleep deprivation (SD) may exert various deleterious effects. In this study, we aimed to examine the adverse behavioral and hormonal effects of SD and a potential treatment with Plant-derived nanoparticle treatment - cocc 30c. The study was a 4-arm trial with randomization and double-blinding of verum and placebo treatments. SD was induced by using the Multiple Platform Method for 48 h. The effects of SD were evaluated behaviorally (pre-pulse inhibition (PPI), startle response and rotor-rod) at baseline as well as at 6, 12, 24h, and 14 days post deprivation. cocc 30c treatment was administrated Per Os every three hours starting immediately after baseline tests and for a period of 24h. On day 14, blood samples were taken and serum levels of corticosterone, testosterone, serotonin and leptin were tested. We found that cocc 30c improved PPI 12 and 24h post deprivation, likewise, cocc 30c improved motor learning. On day 14 SD led to increased startle response that was ameliorated by cocc 30c. Likewise, SD led to increased levels of corticosterone and serotonin while decreasing testosterone and leptin. Interestingly, cocc 30c treatment has moderated these hormonal alterations. We conclude that the treatment with cocc 30c recovers both short-term behavioral and the long-term hormonal modulations following SD.

Circadian disruption, Per3, and human cytokine secretion.

Circadian disruption has been linked with inflammation, an established cancer risk factor. Per3 clock gene polymorphisms have also been associated with circadian disruption and with increased cancer risk. Patients completed a questionnaire and provided a blood sample prior to undergoing a colonoscopy (n = 70). Adjusted mean serum cytokine concentrations (IL-6, TNF-alpha, gamma-INF, IL-1ra, IL-1-beta, VEGF) were compared among patients with high and low scores for fatigue (Multidimensional Fatigue Inventory), depressive symptoms (Beck Depression Inventory II), or sleep disruption (Pittsburgh Sleep Quality Index), or among patients with different Per3 clock gene variants. Poor sleep was associated with elevated VEGF, and fatigue-related reduced activity was associated with elevated TNF-alpha concentrations. Participants with the 4/5 or 5/5 Per3 variable tandem repeat sequence had elevated IL-6 concentrations compared to those with the 4/4 genotype. Biological processes linking circadian disruption with cancer remain to be elucidated. Increased inflammatory cytokine secretion may play a role.

Late, but not early, wake therapy reduces morning plasma melatonin: relationship to mood in Premenstrual Dysphoric Disorder.

Wake therapy improves mood in Premenstrual Dysphoric Disorder (PMDD), a depressive disorder in DSM-IV. We tested the hypothesis that the therapeutic effect of wake therapy in PMDD is mediated by altering sleep phase with melatonin secretion. We measured plasma melatonin every 30 min (18:00-09:00 h) in 19 PMDD and 18 normal control (NC) women during mid-follicular (MF) and late luteal (LL) menstrual cycle phases, and during LL interventions with early wake therapy (EWT) (sleep 03:00-07:00 h)(control condition) vs. late wake therapy (LWT) (sleep 21:00-01:00 h)(active condition). Melatonin offset was delayed and duration was longer in the symptomatic LL vs. asymptomatic MF phase in both NC and PMDD subjects. LWT, but not EWT, advanced offset and shortened duration vs. the LL baseline, although they improved mood equally. Later baseline LL morning melatonin offset was associated with more depressed mood in PMDD patients, and longer melatonin duration in the MF phase predicted greater mood improvement following LWT. That LWT, but not EWT, advanced melatonin offset and shortened duration while they were equally effective in improving mood suggests that decreasing morning melatonin secretion is not necessary for the therapeutic effects of wake therapy in PMDD.

Hypothalamic thyrotropin-releasing hormone mRNA responses to hypothyroxinemia induced by sleep deprivation.

Sleep deprivation in rats results in progressive declines in circulating concentrations of both total and free thyroxine (T(4)) and triiodothyronine (T(3)) without an expected increase in plasma thyroid-stimulating hormone (TSH). Administration of thyrotropin-releasing hormone (TRH) results in appropriate increases in plasma TSH, free T(4), and free T(3) across experimental days, suggesting deficient endogenous TRH production and/or release. This study examined transcriptional responses related to TRH regulation following sleep deprivation. In situ hybridization was used to detect and quantitate expression of mRNAs encoding prepro-TRH and 5'-deiodinase type II (5'-DII) in brain sections of six rats sleep deprived for 16-21 days, when there was marked hypothyroxinemia, and in sections from animals yoked to the experimental protocol as well as from sham controls. TRH transcript levels in the paraventricular nucleus (PVN) were essentially unchanged at 15-16 days but increased to about threefold control levels in three of four rats sleep deprived for 20-21 days, a change comparable to that typically found in prolonged experimental hypothyroidism. There was no evidence for suppression of 5'-DII mRNA levels, which would be a sign of T(3) feedback downregulation of neurons in the PVN. A failure to increase serum TSH in response to hypothyroxinemia and to increased prepro-TRH mRNA expression indicates that alterations in posttranscriptional stages of TRH synthesis, processing, or release likely mediate the central hypothyroidism induced by sleep deprivation.